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Growth stimulation of colorectal carcinoma cells via the c‐kit receptor is inhibited by TGF‐β1
Author(s) -
Bellone Graziella,
Silvestri Stefania,
Artusio Elisa,
Tibaudi Daniela,
Turletti Anna,
Geuna Massimo,
Giachino Claudia,
Valente Guido,
Emanuelli Giorgio,
Rodeck Ulrich
Publication year - 1997
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199707)172:1<1::aid-jcp1>3.0.co;2-s
Subject(s) - autocrine signalling , stem cell factor , cancer research , cell growth , biology , proto oncogene proteins c kit , transforming growth factor , receptor tyrosine kinase , receptor , growth factor , cell culture , cell , stem cell , medicine , haematopoiesis , signal transduction , endocrinology , microbiology and biotechnology , genetics , biochemistry
Activation of the receptor tyrosine kinase c‐kit by the kit‐ligand, also known as stem cell factor (SCF), is essential to melanocyte and germ cell development and during the early stages of hematopoiesis. Deregulated expression of c‐kit has been reported in malignancies affecting these lineages, i.e., myeloid leukemias, melanomas, and germ cell tumors. In addition, c‐kit and SCF are coexpressed in some breast and colorectal cancer (CRC) cells, raising the question of whether c‐kit serves an autocrine role in normal or malignant epithelial tissues. In this study, we demonstrate that human colorectal carcinomas, but not normal colorectal mucosa cells, coexpress SCF and c‐kit in situ. Expression of c‐kit was also observed in mucosa adjacent to colorectal tumor tissue. Consistent with a growth‐regulatory role of SCF in CRC cells, exogenous SCF stimulated anchorage‐dependent and anchorage‐independent growth in four out of five CRC cell lines. Exogenous transforming growth factor (TGF)‐β1 added at nanomolar concentrations to HT‐29 CRC cells, which express the type I, II, and III TGF‐β receptors, downregulated c‐kit expression to background levels and inhibited c‐kit–dependent proliferation. Similarly, TGF‐β1 inhibited SCF‐dependent proliferation of three first‐passage CRC cell lines. In summary, expression of the potential autocrine SCF/c‐kit axis is a tumor‐associated phenomenon in colorectal cancer that can be suppressed by TGF‐β1 in TGF‐β–responsive CRC cells. J. Cell. Physiol. 172:1–11, 1997. © 1997 Wiley‐Liss, Inc.