Interaction between stromal cells and tumor cells induces chemoresistance and matrix metalloproteinase secretion.
Interaction between stromal cells and tumor cells induces chemoresistance and matrix metalloproteinase secretion.
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基质细胞和肿瘤细胞之间的相互作用诱导化疗耐药性和基质金属蛋白酶分泌。
DOI：
10.1111/j.1749-6632.1999.tb07750.x
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发表时间：
1999
影响因子：
5.2
通讯作者：
Lokeshwar,BL
中科院分区：
文献类型：
--
作者：
Zhu,B;Block,NL;Lokeshwar,BL
转移性前列腺癌对大多数细胞毒性化疗药物具有耐药性。在细胞或分子水平上，癌细胞对化疗药物产生耐药性是一个复杂的现象。在许多调节抗癌药物化学敏感性的非突变机制中，细胞-细胞和细胞-细胞外基质（ECM）相互作用被认为是重要的。3-5由于正常前列腺上皮细胞的生存依赖于与基质细胞和ECM的相互作用，因此可能认为基质细胞或其释放的因子也可能改变肿瘤细胞对抗癌药物的反应。此外，肿瘤细胞在改变健康基质以促进肿瘤细胞生长、侵袭和转移方面的作用也刚刚被揭示。此外，人们早就知道，生长在不同转移部位的肿瘤对化疗药物的细胞毒性作用并不同样敏感。8,9我们验证了两个假设：(1)体内转移性肿瘤对抗癌药物反应的差异是由于肿瘤细胞与其周围正常细胞的相互作用；因此，通过在体外创造这些条件我们应该能够在体外重现一些观察到的差异。(2)肿瘤细胞通过诱导基质细胞和内皮细胞分泌基质降解酶来修饰基质细胞和内皮细胞，使其有利于侵袭和转移。通过将肿瘤细胞与从原发肿瘤部位（前列腺）和远处转移部位（如肺）分离的基质细胞共培养，这些假设在前列腺肿瘤细胞上得到了验证。使用的药物为紫杉醇和CMT-3（6，脱氧，6-二甲基，4-去二甲氨基四环素）。CMT-3是一种具有多种细胞靶点的新型细胞毒性化合物。10-12在培养条件培养基中，采用种特异性酶免疫测定法（ELISA）检测肿瘤细胞对基质细胞和内皮细胞分泌MMP模式的影响。
Metastatic prostate cancer is resistant to most cytotoxic chemotherapeutic drugs. 1, 2 At the cellular or molecular level the development of resistance to chemotherapeutic drugs by cancer cells is a complex phenomenon. Among the many nonmutational mechanisms that regulate chemosensitivity to anticancer drugs, cell-cell and cell-extracellular matrix (ECM) interactions are believed to be important. 3–5 Because the normal prostatic epithelial cells rely on their interactions with stromal cells and the ECM for their survival, it may be argued that stromal cells or the factors released by them may also alter the response of tumor cells to anticancer drugs. 6 Moreover, the role of tumor cells in modifying the healthy stroma to facilitate tumor cell growth, invasion, and metastasis is also just being unraveled. 7 Furthermore, it has long been known that tumors growing in different metastatic sites are not equally sensitive to cytotoxic actions of chemotherapy drugs. 8, 9We tested two hypothesis:(1) The differences in the responses of the metastatic tumors to anticancer drugs in vivo is due to the interaction of tumor cells with the normal cells that surround them; and therefore, by creating these conditions in vitro we should be able to reproduce some of the observed differences in vitro.(2) Tumor cells modify the stromal cells and endothelial cells to their advantage for invasion and metastasis by inducing them to secrete matrix-degrading enzymes. These hypotheses were tested on prostate tumor cells by coculturing tumor cells with stromal cells isolated from both the primary tumor site (prostate) and a distant metastatic site (eg, lung). The drugs used were Taxol and CMT-3 (6, deoxy, 6-dimethyl, 4-dedimethylamino tetracycline). CMT-3 is aa novel cytotoxic compound with multiple cellular targets. 10–12 The effect of tumor cells on the pattern of MMP secretion by stromal cells and endothelial cells was examined in culture-conditioned medium using species-specific enzyme immunoassays (ELISA).