Research progress of cancer<b>-</b>associated fibroblasts in breast cancer metastasis and drug resistance_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LIU Guangjin ¹ , GUO Mengjie ¹ , LI Jiaqi ² ,  LI Yuandong ³

1. Department of First Clinical Medicine, Shanxi Medical University, Taiyuan 030001, P. R. China;
2. School of Nursing, Shanxi Medical University, Taiyuan 030001, P. R. China;
3. Department of Breast Surgery, The First Hospital of Shanxi Medical University, Taiyuan 030001, P. R. China;

Corresponding author：

LI Yuandong, Email: 458387465@qq.com

Keywords：

breast cancer; cancer-associated fibroblasts; tumor microenvironment; neoplasm metastasis; drug resistance

DOI：

10.7507/1007-9424.202309054

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To summarize the latest research progress and related mechanisms of cancer-associated fibroblasts (CAFs) in invasion, metastasis and drug resistance of breast cancer, so as to seek the best treatment strategy for patients with breast cancer metastasis and drug resistance. Method The literatures about CAFs research in breast cancer in recent years were searched and summarized. Results CAFs was the main stromal cell in tumor microenvironment (TME). By changing TME, the biological characteristics of CAFs could be changed and the growth and invasion of breast cancer cells could be induced. CAFs in breast cancer promotes the invasion and metastasis of breast cancer cells by interacting with inflammatory factors and promoting the formation of pre-transplantation ecosystems, and CAFs also mediates chemotherapy resistance to breast cancer, target resistance, endocrine resistance, and radiation resistance through the secretion of various cellular factors. Conclusions At present, some progress has been made in the research of CAFs in breast cancer, but there is still a certain gap to clinical application CAFs has a variety of functional phenotypes, so it is necessary to identify and characterize specific CAFs subtypes when studying new anti-CAFs therapeutic strategies. It has been proved that CAFs has great potential as a specific target for breast cancer treatment, but CAFs still lacks specific biomarkers. Therefore, an in-depth understanding of the biological characteristics and heterogeneity of CAFs can provide a reliable theoretical basis for developing drugs targeting CAFs.

Citation： LIU Guangjin, GUO Mengjie, LI Jiaqi, LI Yuandong. Research progress of cancer-associated fibroblasts in breast cancer metastasis and drug resistance. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2023, 30(12): 1529-1536. doi: 10.7507/1007-9424.202309054 Copy

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9.	Biffi G, Tuveson DA. Diversity and biology of cancer-associated fibroblasts. Physiol Rev, 2021, 101(1): 147-176.
10.	Tang S, Yang L, Tang X, et al. The role of oxidized atm in the regulation of oxidative stress-induced energy metabolism reprogramming of cafs. Cancer Lett, 2014, 353(2): 133-144.
11.	Costa A, Kieffer Y, Scholer-Dahirel A, et al. Fibroblast heterogeneity and immunosuppressive environment in human breast cancer. Cancer Cell, 2018, 33(3): 463-479.
12.	Nurmik M, Ullmann P, Rodriguez F, et al. In search of definitions: cancer-associated fibroblasts and their markers. Int J Cancer, 2020, 146(4): 895-905.
13.	Hu D, Li Z, Zheng B, et al. Cancer-associated fibroblasts in breast cancer: challenges and opportunities. Cancer Commun (Lond), 2022, 42(5): 401-434.
14.	Kanzaki R, Pietras K. Heterogeneity of cancer-associated fibroblasts: opportunities for precision medicine. Cancer Sci, 2020, 111(8): 2708-2717.
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16.	Plava J, Cihova M, Burikova M, et al. Recent advances in understanding tumor stroma- mediated chemoresistance in breast cancer. Mol Cancer, 2019, 18(1): 67.
17.	Wang B, Liu W, Liu C, et al. Cancer-associated fibroblasts promote radioresistance of breast cancer cells via the HGF/c-Met signaling pathway. Int J Radiat Oncol Biol Phys, 2023, 116(3): 640-654.
18.	Guo Z, Zhang H, Fu Y, et al. Cancer-associated fibroblasts induce growth and radioresistance of breast cancer cells through paracrine IL-6. Cell Death Discov, 2023, 9(1): 6.
19.	Kang S, Tanaka T, Kishimoto T. Therapeutic uses of anti-interleukin-6 receptor antibody. Int Immunol, 2015, 27(1): 21-29.
20.	Su S, Chen J, Yao H, et al. CD10⁺GPR77⁺ cancer-associated fibroblasts promote cancer formation and chemoresistance by sustaining cancer stemness. Cell, 2018, 172(4): 841-856.
21.	Maia A, Gu Z, Koch A, et al. IFNβ1 secreted by breast cancer cells undergoing chemotherapy reprograms stromal fibroblasts to support tumour growth after treatment. Mol Oncol, 2021, 15(5): 1308-1329.
22.	Al-Tweigeri T, AlRaouji NN, Tulbah A, et al. High AUF1 level in stromal fibroblasts promotes carcinogenesis and chemoresistance and predicts unfavorable prognosis among locally advanced breast cancer patients. Breast Cancer Res, 2022, 24(1): 46.
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28.	Fernández-Nogueira P, Mancino M, Fuster G, et al. Tumor-associated fibroblasts promote HER2-targeted therapy resistance through FGFR2 activation. Clin Cancer Res, 2020, 26(6): 1432-1448.
29.	Rivas EI, Linares J, Zwick M, et al. Targeted immunotherapy against distinct cancer- associated fibroblasts overcomes treatment resistance in refractory HER2⁺ breast tumors. Nat Commun, 2022, 13(1): 5310.
30.	Du R, Zhang X, Lu X, et al. PDPN positive CAFs contribute to HER2 positive breast cancer resistance to trastuzumab by inhibiting antibody-dependent NK cell-mediated cytotoxicity. Drug Resist Updat, 2023 May: 68: 100947. doi: 10.1016/j.drup.2023.100947.
31.	Brechbuhl HM, Finlay-Schultz J, Yamamoto TM, et al. Fibroblast subtypes regulate responsiveness of luminal breast cancer to estrogen. Clin Cancer Res, 2017, 23(7): 1710-1721.
32.	Gao Y, Li X, Zeng C, et al. CD63⁺ cancer-associated fibroblasts confer tamoxifen resistance to breast cancer cells through exosomal miR-22. Adv Sci (Weinh), 2020, 7(21): 2002518.
33.	Chandra Jena B, Kanta Das C, Banerjee I, et al. Paracrine TGF-β1 from breast cancer contributes to chemoresistance in cancer associated fibroblasts via upregulation of the p44/42 MAPK signaling pathway. Biochem Pharmacol, 2021 Apr: 186: 114474. doi: 10.1016/j.bcp.2021.114474.
34.	Marx V. Tracking metastasis and tricking cancer. Nature, 2013, 494(7435): 133-136.
35.	Kim MY. Breast cancer metastasis. Adv Exp Med Biol, 2021, 1187: 183-240.
36.	Zhang Y, Yang P, Wang XF. Microenvironmental regulation of cancer metastasis by miRNAs. Trends Cell Biol, 2014, 24(3): 153-160.
37.	Bussard KM, Mutkus L, Stumpf K, et al. Tumor-associated stromal cells as key contributors to the tumor microenvironment. Breast Cancer Res, 2016, 18(1): 84.
38.	Djurec M, Graña O, Lee A, et al. Saa3 is a key mediator of the protumorigenic properties of cancer-associated fibroblasts in pancreatic tumors. Proc Natl Acad Sci U S A, 2018, 115(6): E1147-E1156.
39.	Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell, 2004, 116(2): 281-297.
40.	Guo J, Gong G, Zhang B. MiR-539 acts as a tumor suppressor by targeting epidermal growth factor receptor in breast cancer. Sci Rep, 2018, 8(1): 2073.
41.	Chatterjee A, Jana S, Chatterjee S, et al. MicroRNA-222 reprogrammed cancer-associated fibroblasts enhance growth and metastasis of breast cancer. Br J Cancer, 2019, 121(8): 679-689.
42.	Wu HJ, Hao M, Yeo SK, et al. FAK signaling in cancer-associated fibroblasts promotes breast cancer cell migration and metastasis by exosomal miRNAs-mediated intercellular communication. Oncogene, 2020, 39(12): 2539-2549.
43.	Afshar-Kharghan V. The role of the complement system in cancer. J Clin Invest, 2017, 127(3): 780-789.
44.	Zha H, Wang X, Zhu Y, et al. Intracellular activation of complement C3 leads to PD-L1 antibody treatment resistance by modulating tumor-associated macrophages. Cancer Immunol Res, 2019, 7(2): 193-207.
45.	Shu C, Zha H, Long H, et al. C3a-C3aR signaling promotes breast cancer lung metastasis via modulating carcinoma associated fibroblasts. J Exp Clin Cancer Res, 2020, 39(1): 11.
46.	Aiello NM, Maddipati R, Norgard RJ, et al. EMT subtype influences epithelial plasticity and mode of cell migration. Dev Cell, 2018, 45(6): 681-695.
47.	Schwager SC, Young KM, Hapach LA, et al. Weakly migratory metastatic breast cancer cells activate fibroblasts via microvesicle-Tg2 to facilitate dissemination and metastasis. Elife, 2022, 11: e74433.
48.	Li Q, Lv X, Han C, et al. Enhancer reprogramming promotes the activation of cancer-associated fibroblasts and breast cancer metastasis. Theranostics, 2022, 12(17): 7491-7508.
49.	Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell, 2011, 144(5): 646-674.
50.	Kalluri R. The biology and function of fibroblasts in cancer. Nat Rev Cancer, 2016, 16(9): 582-598.
51.	Sharon Y, Raz Y, Cohen N, et al. Tumor-derived osteopontin reprograms normal mammary fibroblasts to promote inflammation and tumor growth in breast cancer. Cancer Res, 2015, 75(6): 963-973.
52.	Franchi L, Muñoz-Planillo R, Núñez G. Sensing and reacting to microbes through the inflammasomes. Nat Immunol, 2012, 13(4): 325-332.
53.	Henao-Mejia J, Elinav E, Strowig T, et al. Inflammasomes: far beyond inflammation. Nat Immunol, 2012, 13(4): 321-324.
54.	Bruchard M, Mignot G, Derangère V, et al. Chemotherapy-triggered cathepsin B release in myeloid-derived suppressor cells activates the Nlrp3 inflammasome and promotes tumor growth. Nat Med, 2013, 19(1): 57-64.
55.	Ershaid N, Sharon Y, Doron H, et al. NLRP3 inflammasome in fibroblasts links tissue damage with inflammation in breast cancer progression and metastasis. Nat Commun, 2019, 10(1): 4375.
56.	Liu Y, Cao X. Characteristics and significance of the pre-metastatic niche. Cancer Cell, 2016, 30(5): 668-681.
57.	Peinado H, Zhang H, Matei IR, et al. Pre-metastatic niches: organ-specific homes for metastases. Nat Rev Cancer, 2017, 17(5): 302-317.
58.	Zeng H, Hou Y, Zhou X, et al. Cancer-associated fibroblasts facilitate premetastatic niche formation through lncRNA SNHG5-mediated angiogenesis and vascular permeability in breast cancer. Theranostics, 2022, 12(17): 7351-7370.
59.	Seyfried TN, Huysentruyt LC. On the origin of cancer metastasis. Crit Rev Oncog, 2013, 18(1-2): 43-73.
60.	Poudineh M, Sargent EH, Pantel K, et al. Profiling circulating tumour cells and other biomarkers of invasive cancers. Nat Biomed Eng, 2018, 2(2): 72-84.
61.	Ortiz-Otero N, Clinch AB, Hope J, et al. Cancer associated fibroblasts confer shear resistance to circulating tumor cells during prostate cancer metastatic progression. Oncotarget, 2020, 11(12): 1037-1050.
62.	Pietras K, Östman A. Hallmarks of cancer: interactions with the tumor stroma. Exp Cell Res, 2010, 316(8): 1324-1331.
63.	Lu T, Oomens L, Terstappen LWMM, et al. In vivo detection of circulating cancer-associated fibroblasts in breast tumor mouse xenograft: impact of tumor stroma and chemotherapy. Cancers (Basel), 2023, 15(4): 1127. doi: 10.3390/cancers15041127.

1. Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2022. CA Cancer J Clin, 2022, 72(1): 7-33.
2. Giaquinto AN, Sung H, Miller KD, et al. Breast cancer statistics, 2022. CA Cancer J Clin, 2022, 72(6): 524-541.
3. Chandra RA, Keane FK, Voncken FEM, et al. Contemporary radiotherapy: present and future. Lancet, 2021, 398(10295): 171-184.
4. Hinshaw DC, Shevde LA. The tumor microenvironment innately modulates cancer progression. Cancer Res, 2019, 79(18): 4557-4566.
5. Mao X, Xu J, Wang W, et al. Crosstalk between cancer-associated fibroblasts and immune cells in the tumor microenvironment: new findings and future perspectives. Mol Cancer, 2021, 20(1): 131.
6. Ermakov MS, Nushtaeva AA, Richter VA, et al. Cancer-associated fibroblasts and their role in tumor progression. Vavilovskii Zhurnal Genet Selektsii, 2022, 26(1): 14-21.
7. Xiang X, Niu YR, Wang ZH, et al. Cancer-associated fibroblasts: Vital suppressors of the immune response in the tumor microenvironment. Cytokine Growth Factor Rev, 2022, 67: 35-48.
8. Sahai E, Astsaturov I, Cukierman E, et al. A framework for advancing our understanding of cancer-associated fibroblasts. Nat Rev Cancer, 2020, 20(3): 174-186.
9. Biffi G, Tuveson DA. Diversity and biology of cancer-associated fibroblasts. Physiol Rev, 2021, 101(1): 147-176.
10. Tang S, Yang L, Tang X, et al. The role of oxidized atm in the regulation of oxidative stress-induced energy metabolism reprogramming of cafs. Cancer Lett, 2014, 353(2): 133-144.
11. Costa A, Kieffer Y, Scholer-Dahirel A, et al. Fibroblast heterogeneity and immunosuppressive environment in human breast cancer. Cancer Cell, 2018, 33(3): 463-479.
12. Nurmik M, Ullmann P, Rodriguez F, et al. In search of definitions: cancer-associated fibroblasts and their markers. Int J Cancer, 2020, 146(4): 895-905.
13. Hu D, Li Z, Zheng B, et al. Cancer-associated fibroblasts in breast cancer: challenges and opportunities. Cancer Commun (Lond), 2022, 42(5): 401-434.
14. Kanzaki R, Pietras K. Heterogeneity of cancer-associated fibroblasts: opportunities for precision medicine. Cancer Sci, 2020, 111(8): 2708-2717.
15. Cords L, Tietscher S, Anzeneder T, et al. Cancer-associated fibroblast classification in single-cell and spatial proteomics data. Nat Commun, 2023, 14(1): 4294.
16. Plava J, Cihova M, Burikova M, et al. Recent advances in understanding tumor stroma- mediated chemoresistance in breast cancer. Mol Cancer, 2019, 18(1): 67.
17. Wang B, Liu W, Liu C, et al. Cancer-associated fibroblasts promote radioresistance of breast cancer cells via the HGF/c-Met signaling pathway. Int J Radiat Oncol Biol Phys, 2023, 116(3): 640-654.
18. Guo Z, Zhang H, Fu Y, et al. Cancer-associated fibroblasts induce growth and radioresistance of breast cancer cells through paracrine IL-6. Cell Death Discov, 2023, 9(1): 6.
19. Kang S, Tanaka T, Kishimoto T. Therapeutic uses of anti-interleukin-6 receptor antibody. Int Immunol, 2015, 27(1): 21-29.
20. Su S, Chen J, Yao H, et al. CD10⁺GPR77⁺ cancer-associated fibroblasts promote cancer formation and chemoresistance by sustaining cancer stemness. Cell, 2018, 172(4): 841-856.
21. Maia A, Gu Z, Koch A, et al. IFNβ1 secreted by breast cancer cells undergoing chemotherapy reprograms stromal fibroblasts to support tumour growth after treatment. Mol Oncol, 2021, 15(5): 1308-1329.
22. Al-Tweigeri T, AlRaouji NN, Tulbah A, et al. High AUF1 level in stromal fibroblasts promotes carcinogenesis and chemoresistance and predicts unfavorable prognosis among locally advanced breast cancer patients. Breast Cancer Res, 2022, 24(1): 46.
23. Lawal B, Wu AT, Chen CH, et al. Identification of INFG/STAT1/NOTCH3 as γ-Mangostin’s potential targets for overcoming doxorubicin resistance and reducing cancer-associated fibroblasts in triple-negative breast cancer. Biomed Pharmacother, 2023 Jul: 163: 114800. doi: 10.1016/j.biopha.2023.114800.
24. Burstein HJ. The distinctive nature of HER2-positive breast cancers. N Engl J Med, 2005, 353(16): 1652-1654.
25. von Minckwitz G, Procter M, de Azambuja E, et al. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med, 2017, 377(2): 122-131.
26. Ahmed S, Sami A, Xiang J. HER2-directed therapy: current treatment options for HER2- positive breast cancer. Breast Cancer, 2015, 22(2): 101-116.
27. Martin M, López-Tarruella S. Emerging therapeutic options for HER2-positive breast cancer. Am Soc Clin Oncol Educ Book, 2016, 35: e64-e70.
28. Fernández-Nogueira P, Mancino M, Fuster G, et al. Tumor-associated fibroblasts promote HER2-targeted therapy resistance through FGFR2 activation. Clin Cancer Res, 2020, 26(6): 1432-1448.
29. Rivas EI, Linares J, Zwick M, et al. Targeted immunotherapy against distinct cancer- associated fibroblasts overcomes treatment resistance in refractory HER2⁺ breast tumors. Nat Commun, 2022, 13(1): 5310.
30. Du R, Zhang X, Lu X, et al. PDPN positive CAFs contribute to HER2 positive breast cancer resistance to trastuzumab by inhibiting antibody-dependent NK cell-mediated cytotoxicity. Drug Resist Updat, 2023 May: 68: 100947. doi: 10.1016/j.drup.2023.100947.
31. Brechbuhl HM, Finlay-Schultz J, Yamamoto TM, et al. Fibroblast subtypes regulate responsiveness of luminal breast cancer to estrogen. Clin Cancer Res, 2017, 23(7): 1710-1721.
32. Gao Y, Li X, Zeng C, et al. CD63⁺ cancer-associated fibroblasts confer tamoxifen resistance to breast cancer cells through exosomal miR-22. Adv Sci (Weinh), 2020, 7(21): 2002518.
33. Chandra Jena B, Kanta Das C, Banerjee I, et al. Paracrine TGF-β1 from breast cancer contributes to chemoresistance in cancer associated fibroblasts via upregulation of the p44/42 MAPK signaling pathway. Biochem Pharmacol, 2021 Apr: 186: 114474. doi: 10.1016/j.bcp.2021.114474.
34. Marx V. Tracking metastasis and tricking cancer. Nature, 2013, 494(7435): 133-136.
35. Kim MY. Breast cancer metastasis. Adv Exp Med Biol, 2021, 1187: 183-240.
36. Zhang Y, Yang P, Wang XF. Microenvironmental regulation of cancer metastasis by miRNAs. Trends Cell Biol, 2014, 24(3): 153-160.
37. Bussard KM, Mutkus L, Stumpf K, et al. Tumor-associated stromal cells as key contributors to the tumor microenvironment. Breast Cancer Res, 2016, 18(1): 84.
38. Djurec M, Graña O, Lee A, et al. Saa3 is a key mediator of the protumorigenic properties of cancer-associated fibroblasts in pancreatic tumors. Proc Natl Acad Sci U S A, 2018, 115(6): E1147-E1156.
39. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell, 2004, 116(2): 281-297.
40. Guo J, Gong G, Zhang B. MiR-539 acts as a tumor suppressor by targeting epidermal growth factor receptor in breast cancer. Sci Rep, 2018, 8(1): 2073.
41. Chatterjee A, Jana S, Chatterjee S, et al. MicroRNA-222 reprogrammed cancer-associated fibroblasts enhance growth and metastasis of breast cancer. Br J Cancer, 2019, 121(8): 679-689.
42. Wu HJ, Hao M, Yeo SK, et al. FAK signaling in cancer-associated fibroblasts promotes breast cancer cell migration and metastasis by exosomal miRNAs-mediated intercellular communication. Oncogene, 2020, 39(12): 2539-2549.
43. Afshar-Kharghan V. The role of the complement system in cancer. J Clin Invest, 2017, 127(3): 780-789.
44. Zha H, Wang X, Zhu Y, et al. Intracellular activation of complement C3 leads to PD-L1 antibody treatment resistance by modulating tumor-associated macrophages. Cancer Immunol Res, 2019, 7(2): 193-207.
45. Shu C, Zha H, Long H, et al. C3a-C3aR signaling promotes breast cancer lung metastasis via modulating carcinoma associated fibroblasts. J Exp Clin Cancer Res, 2020, 39(1): 11.
46. Aiello NM, Maddipati R, Norgard RJ, et al. EMT subtype influences epithelial plasticity and mode of cell migration. Dev Cell, 2018, 45(6): 681-695.
47. Schwager SC, Young KM, Hapach LA, et al. Weakly migratory metastatic breast cancer cells activate fibroblasts via microvesicle-Tg2 to facilitate dissemination and metastasis. Elife, 2022, 11: e74433.
48. Li Q, Lv X, Han C, et al. Enhancer reprogramming promotes the activation of cancer-associated fibroblasts and breast cancer metastasis. Theranostics, 2022, 12(17): 7491-7508.
49. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell, 2011, 144(5): 646-674.
50. Kalluri R. The biology and function of fibroblasts in cancer. Nat Rev Cancer, 2016, 16(9): 582-598.
51. Sharon Y, Raz Y, Cohen N, et al. Tumor-derived osteopontin reprograms normal mammary fibroblasts to promote inflammation and tumor growth in breast cancer. Cancer Res, 2015, 75(6): 963-973.
52. Franchi L, Muñoz-Planillo R, Núñez G. Sensing and reacting to microbes through the inflammasomes. Nat Immunol, 2012, 13(4): 325-332.
53. Henao-Mejia J, Elinav E, Strowig T, et al. Inflammasomes: far beyond inflammation. Nat Immunol, 2012, 13(4): 321-324.
54. Bruchard M, Mignot G, Derangère V, et al. Chemotherapy-triggered cathepsin B release in myeloid-derived suppressor cells activates the Nlrp3 inflammasome and promotes tumor growth. Nat Med, 2013, 19(1): 57-64.
55. Ershaid N, Sharon Y, Doron H, et al. NLRP3 inflammasome in fibroblasts links tissue damage with inflammation in breast cancer progression and metastasis. Nat Commun, 2019, 10(1): 4375.
56. Liu Y, Cao X. Characteristics and significance of the pre-metastatic niche. Cancer Cell, 2016, 30(5): 668-681.
57. Peinado H, Zhang H, Matei IR, et al. Pre-metastatic niches: organ-specific homes for metastases. Nat Rev Cancer, 2017, 17(5): 302-317.
58. Zeng H, Hou Y, Zhou X, et al. Cancer-associated fibroblasts facilitate premetastatic niche formation through lncRNA SNHG5-mediated angiogenesis and vascular permeability in breast cancer. Theranostics, 2022, 12(17): 7351-7370.
59. Seyfried TN, Huysentruyt LC. On the origin of cancer metastasis. Crit Rev Oncog, 2013, 18(1-2): 43-73.
60. Poudineh M, Sargent EH, Pantel K, et al. Profiling circulating tumour cells and other biomarkers of invasive cancers. Nat Biomed Eng, 2018, 2(2): 72-84.
61. Ortiz-Otero N, Clinch AB, Hope J, et al. Cancer associated fibroblasts confer shear resistance to circulating tumor cells during prostate cancer metastatic progression. Oncotarget, 2020, 11(12): 1037-1050.
62. Pietras K, Östman A. Hallmarks of cancer: interactions with the tumor stroma. Exp Cell Res, 2010, 316(8): 1324-1331.
63. Lu T, Oomens L, Terstappen LWMM, et al. In vivo detection of circulating cancer-associated fibroblasts in breast tumor mouse xenograft: impact of tumor stroma and chemotherapy. Cancers (Basel), 2023, 15(4): 1127. doi: 10.3390/cancers15041127.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Research progress of cancer-associated fibroblasts in breast cancer metastasis and drug resistance

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