IN-VIVO AND IN-VITRO INVASIVENESS OF A RAT COLON-CANCER CELL-LINE MAINTAINING E-CADHERIN EXPRESSION - AN ENHANCING ROLE OF TUMOR-ASSOCIATED MYOFIBROBLASTS

IN-VIVO AND IN-VITRO INVASIVENESS OF A RAT COLON-CANCER CELL-LINE MAINTAINING E-CADHERIN EXPRESSION - AN ENHANCING ROLE OF TUMOR-ASSOCIATED MYOFIBROBLASTS
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DOI:
10.1002/ijc.2910560410
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发表时间:
1994-02-15
影响因子:
6.4
通讯作者:
MARTIN, F
MARTIN, F
中科院分区:
医学1区
文献类型:
--
作者:
DIMANCHEBOITREL, MT;VAKAET, L;MARTIN, F

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在不同的细胞系统中,发现E-cadherin(一种参与上皮细胞的Ca 2+依赖性同源细胞-细胞附着的分子)的表达与体外侵入细胞外基质凝胶或正常组织的能力之间存在反比关系。DHD/K12/TRb(PROb)细胞,保持作为一个细胞系来自大鼠结肠癌,均匀表达在体外免疫反应性E-钙粘蛋白,这是功能性的细胞解离-再结合试验中所示。在3种不同的体外试验中发现PROb细胞是非侵入性的。然而,由s.c.将PROb细胞注射到同基因BD-IX大鼠中是侵入性的,尽管PROb鳗鱼在肿瘤中维持E-钙粘蛋白表达。来自新鲜分离的PROb肿瘤的细胞显示,不仅PROb细胞,而且肿瘤相关的肌成纤维细胞,并且能够穿过基质胶涂覆的过滤器。PROb肿瘤确实被许多肌成纤维细胞浸润,主要位于肿瘤的侵袭边缘。来自肿瘤浸润性肌成纤维细胞的已建立培养物的细胞能够通过基质胶涂覆的过滤器或进入鸡心碎片赋予PROb细胞侵袭力。PROb细胞在肌成纤维细胞增强的Matrigel侵袭后保持其表达E-cadherin的能力。肿瘤相关的肌成纤维细胞,但不是PROb细胞,分泌72-kDa的胶原酶,其可以在肿瘤细胞侵袭中发挥作用。这些结果强烈表明,来自肿瘤间质的细胞,更具体地说是肌成纤维细胞,可能参与体内上皮肿瘤细胞的侵袭,即使在不同的体外试验中E-钙粘蛋白表达阻止肿瘤细胞的侵袭。(C)1994 Wiley-Liss,Inc.
In various cell systems, an inverse relationship was found between expression of E-cadherin, a molecule involved in the Ca2+-dependent homophylic cell-to-cell attachment of epithelial cells, and the capacity to invade extracellular matrix gels or normal tissues in vitro. DHD/K12/TRb (PROb) cells, maintained as a cell line derived from a rat colon carcinoma, homogeneously expressed in vitro immunoreactive E-cadherin, which was functional as shown in cell dissociation-reassociation assays. PROb cells were found to be non-invasive in 3 different assays in vitro. However, tumors resulting from a s.c. injection of PROb cells into syngeneic BD-IX rats were invasive, although PROb eels maintained E-cadherin expression in the tumors. Cells from a freshly dissociated PROb tumor showed, not only PROb cells but also tumor-associated myofibroblasts and were able to cross a Matrigel-coated filter. PROb tumors were indeed infiltrated by numerous myofibroblasts, mainly located at the invasive edge of the tumor. Cells from an established culture of tumor-infiltrating myofibroblasts were able to confer upon PROb cells invasiveness through Matrigel-coated filter or into chick-heart fragments. PROb cells maintained their capacity to express E-cadherin after myofibroblast-enhanced Matrigel invasion, Tumor-associated myofibroblasts, but not PROb cells, secreted a 72-kDa collagenase that could play a role in tumor-cell invasion. These results strongly suggest that cells from the tumor stroma, and more specifically myofibroblasts, may be involved in the invasiveness of epithelial tumor cells in vivo, even when E-cadherin expression prevents tumor-cell invasiveness in different in vitro assays. (C) 1994 Wiley-Liss, Inc.