INSERM U563, Centre de Physiopathologie de Toulouse-Purpan, Toulouse F-31300, France.
Int J Oncol. 2010 Dec;37(6):1453-61. doi: 10.3892/ijo_00000797.
In breast cancers, the appearance of metastasis is synonymous with poor prognosis. The metastatic process is usually associated with epithelial-mesenchymal transition (EMT) which is often induced by several soluble factors produced either by the tumour cells themselves or by cells constituting the tumour microenvironment. The aim of the present study was to determine whether the mesenchymal properties given by some molecules such as N-cadherin, for instance, could be acquired by cancer cells via the trogocytosis process with cells of the tumour microenvironment. Hospicells are stromal cells which were first isolated from cancer cell aggregates of patients with ovarian cancer. We recently showed that these cells are immunosuppressive for T lymphocyte functions and confer chemoresistance to cancer cells by the transfer of the MDR protein via trogocytosis. In this study, we showed that a mammary cancer cell line (MDA-MB-231) acquires patches of membrane via oncologic trogocytosis with Hospicells. This unidirectional and active process depends on actin polymerization and can be increased via inhibition of the Src family and decreased via inhibition of PI3K. Trogocytosis between Hospicells and MDA-MB-231 does not lead to the direct acquisition of N-cadherin but rather it leads to the production of soluble factor(s) which induce de novo expression of N-cadherin by the cancer cells. The novelty here is that this factor is produced only if cancer cells interact and undergo trogocytosis with Hospicells. This new expression could confer a more invasive phenotype to the cancer cells and thus can explain the correlation of the presence of Hospicells with the number of invaded lymph nodes in patients with mammary adenocarcinoma.
在乳腺癌中，转移的出现意味着预后不良。转移过程通常与上皮间质转化（EMT）有关，EMT 通常是由肿瘤细胞本身或构成肿瘤微环境的细胞产生的几种可溶性因子诱导的。本研究的目的是确定一些分子（例如 N-钙粘蛋白）赋予的间质特性是否可以通过细胞吞噬作用由癌细胞从肿瘤微环境中的细胞获得。Hospicells 是首先从卵巢癌患者的癌细胞聚集体中分离出来的基质细胞。我们最近表明，这些细胞通过细胞吞噬作用将 MDR 蛋白转移给癌细胞，从而对 T 淋巴细胞功能具有免疫抑制作用，并赋予癌细胞化疗耐药性。在这项研究中，我们表明一种乳腺癌细胞系（MDA-MB-231）通过与 Hospicells 的癌性细胞吞噬作用获得膜斑。这个单向且主动的过程依赖于肌动蛋白聚合，可通过抑制 Src 家族增加，通过抑制 PI3K 减少。Hospicells 和 MDA-MB-231 之间的细胞吞噬作用不会直接导致 N-钙粘蛋白的直接获得，而是导致产生可溶性因子，这些因子诱导癌细胞新表达 N-钙粘蛋白。这里的新颖之处在于，只有当癌细胞与 Hospicells 相互作用并发生细胞吞噬作用时，才会产生这种因子。这种新的表达可能使癌细胞具有更具侵袭性的表型，从而可以解释 Hospicells 存在与乳腺腺癌患者淋巴结侵袭数量之间的相关性。
