Bellone G, Carbone A, Sibona N, Bosco O, Tibaudi D, Smirne C, Martone T, Gramigni C, Camandona M, Emanuelli G, Rodeck U
Department of Clinical Physiopathology University of Torino, Italy.
Cancer Res. 2001 Mar 1;61(5):2200-6.
Multiple genetic aberrations contribute to the development of biologically aggressive, clinically malignant colorectal carcinomas (CRCs). Some of these have been linked to inappropriate signaling through the tyrosine kinase moieties of growth factor receptors. We have described previously (G. Bellone et al., J. Cell. Physiol., 172: 1-11, 1997) that human CRCs overexpress both the receptor tyrosine kinase c-kit and its ligand, stem cell factor (SCF), relative to normal mucosa cells, thus establishing an autocrine c-kit-mediated loop. In addition, we noted that exogenous SCF contributes to anchorage-independent growth of HT-29 colon carcinoma cells in semisolid medium. Here, we investigated possible roles of the c-kit/SCF autocrine/paracrine system in survival and invasive capacity of DLD-1 colon carcinoma cells. We report that SCF was required for migration and invasion of DLD-1 cells through reconstituted basement membranes (Matrigel) and up-regulated gelatinase (matrix metalloproteinase-9) activity in DLD-1 cells. Furthermore, we describe that SCF supported survival of DLD-1 cells in growth factor-deprived conditions. These results suggest multiple roles of c-kit activation in support of the malignant phenotype of DLD-1 cells related to growth, survival, migration, and invasive potential.
多种基因畸变促成了具有生物学侵袭性、临床恶性的结直肠癌（CRC）的发展。其中一些与生长因子受体酪氨酸激酶部分的不适当信号传导有关。我们之前已经描述过（G. Bellone等人，《细胞生理学杂志》，172: 1 - 11，1997），相对于正常黏膜细胞，人类结直肠癌中受体酪氨酸激酶c-kit及其配体干细胞因子（SCF）均过度表达，从而建立了一种自分泌的c-kit介导的环路。此外，我们注意到外源性SCF有助于HT - 29结肠癌细胞在半固体培养基中进行不依赖贴壁的生长。在此，我们研究了c-kit/SCF自分泌/旁分泌系统在DLD - 1结肠癌细胞的存活和侵袭能力中可能发挥的作用。我们报告称，SCF是DLD - 1细胞通过重组基底膜（基质胶）迁移和侵袭所必需的，并且上调了DLD - 1细胞中的明胶酶（基质金属蛋白酶 - 9）活性。此外，我们描述了SCF在生长因子缺乏的条件下支持DLD - 1细胞的存活。这些结果表明c-kit激活在支持DLD - 1细胞与生长、存活、迁移和侵袭潜能相关的恶性表型方面具有多种作用。
