Fibroblasts Promote Proliferation and Matrix Invasion of Breast Cancer Cells in Co‐Culture Models
Fibroblasts Promote Proliferation and Matrix Invasion of Breast Cancer Cells in Co‐Culture Models
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共培养模型中成纤维细胞促进乳腺癌细胞增殖和基质侵袭
DOI：
10.1002/adtp.201900121
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发表时间：
2019
影响因子：
4.6
通讯作者：
Tavana, Hossein
中科院分区：
文献类型：
--
作者：
Plaster, Madison;Singh, Sunil;Tavana, Hossein
成纤维细胞是肿瘤微环境中丰富的细胞类型。激活的成纤维细胞，称为癌相关成纤维细胞（CAF），通过生化信号与癌细胞相互作用，使癌细胞增殖、侵袭和对治疗产生耐药性。靶向 CAF-癌细胞相互作用提供了一种阻止癌症进展的策略。使用人乳腺成纤维细胞和三阴性乳腺癌 (TNBC) 细胞的 2D 和 3D 共培养物来研究异型细胞相互作用对 TNBC 细胞基质侵袭增殖的影响。结果表明，分泌趋化因子CXCL12的成纤维细胞显着增强表达趋化因子受体CXCR4的TNBC细胞的增殖。破坏与受体拮抗剂的这种相互作用可以使癌细胞增殖正常化到缺乏这种信号传导的共培养模型。当共培养球体嵌入胶原中时，产生 CXCL12 的成纤维细胞会促进胶原对 TNBC 细胞的侵袭。尽管含有正常成纤维细胞的共培养物也会导致 TNBC 细胞扩散到基质中，但细胞形态学分析和趋化因子受体信号传导的抑制表明，这种扩散是由于成纤维细胞和癌细胞的不相容性导致两种细胞类型从球体中分离。
Fibroblasts are an abundant cell type in tumor microenvironments. Activated fibroblasts, known as carcinoma‐associated fibroblasts (CAFs), interact with cancer cells through biochemical signaling and render cancer cells proliferative, invasive, and resistant to therapeutics. Targeting CAFs–cancer cells interactions offers a strategy to block cancer progression. 2D and 3D co‐cultures of human mammary fibroblasts and triple negative breast cancer (TNBC) cells are used to investigate the impact of heterotypic cellular interactions on the proliferation of matrix invasion of TNBC cells. The results show that fibroblasts secreting a chemokine, CXCL12, significantly enhance proliferation of TNBC cells expressing the chemokine receptor, CXCR4. Disrupting this interaction with a receptor antagonist normalizes cancer cell proliferation to that of a co‐culture model lacking this signaling. When co‐culture spheroids are embedded in collagen, fibroblasts producing CXCL12 promote collagen invasion of TNBC cells. Although co‐cultures containing normal fibroblasts also lead to TNBC cell spreading into the matrix, a morphological analysis of cells and inhibition of chemokine‐receptor signaling shows that this spreading is due to the incompatibility of fibroblasts and cancer cells leading to the segregation of the two cell types from the spheroid.
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影响因子：
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作者：
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DOI：
10.1016/j.bbrc.2007.05.182
发表时间：
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影响因子：
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影响因子：
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