Co-stimulation of gastrointestinal tumour cell growth by gastrin, transforming growth factor α and insulin like growth factor-I

Abstract

Summary Epidermal growth factor receptors and insulin like growth factor-I receptors were co-expressed on two gastric and three colorectal tumour cell lines. Previous studies have shown that gastrin receptors were also expressed at a low level or two of these cell lines. Both TGFa and IGF-I promoted cell growth in all of the cell lines tested. The cell doubling time of a colorectal cell line was reduced from 48 to 30 -34 h. Furthermore the effects of the growth factors were additive. Each growth factor also increased the response of the cells to gastrin, but a combination of both growth factors and gastrin did not further increase growth.The growth of gastrointestinal mucosa is regulated by numerous hormones and growth factors. However the factors controlling growth of tumours arising in these tissues are not as well understood. Previous studies have shown that the hormone gastrin plays a central role in the stimulation of gut tumour proliferation (Townsend et al., 1988;Morris et al., 1989b;Watson et al., 1988Watson et al., , 1989b In a large study with a wide variety of tumours Derynck et al. (1987) showed that EGF receptor and TGFax mRNAs were expressed at higher levels in the tumour than the corresponding normal tissue. In a more recent study concurrent expression of mRNA for TGFa and its receptor was more frequently found in gastric tumours (38%) than in the adjacent normal mucosa (7%). Higher levels of TGFa mRNA were found in tumour than adjacent normal tissue (Bennett et al., 1989 (Gibco, Paisely, Fife). Prior to incubation with the growth factors they were washed twice in serum free medium and plated in 1:1 mixture of Hams F12:Eagle's medium containing 0.1% BSA (Sigma, Poole, Dorset) and left for 4-18 h.Receptor measurements Cells were grown in serum free medium for 48 h prior to receptor measurements. Cells were harvested by rubber policemen, counted and incubated with either radiolabelled IGF-I (10 ng ml-') (Amersham International) or radiolabelled EGF (1O ng ml-') in the presence or absence of a 1,000 fold excess of unlabelled specific and nonspecific ligand (Hoosien et al., 1987

New approaches to therapy of cancers of the stomach, colon and pancreas based on peptide analogs

“…EGF receptors are also expressed in colorectal cancer cell lines. Both TGF-a and IGF-I promote cell growth of colorectal cancer cell lines and increase the response of the cells to gastrin [129]. Karnes et al [160] showed that monoclonal antibody mAb225 against EGF receptors can inhibit the proliferation of some colorectal carcinoma cell lines that co-express TGF-a and EGFR.…”

“…EGF receptors and IGF-I receptors are expressed on human gastric cancer cell lines. Both TGF-a and IGF-I promote cell growth and increase the response of the cells to gastrin [129]. Gastric cancer patients also show higher serum and urinary c-erbB-2 levels than healthy controls [130].…”

Growth Hormone Receptor Expression is Up-Regulated During Tumorigenesis of Human Colorectal Cancer

“…The relation between the IGF system and colorectal cancer has aroused increasing attention. IGF-1 is a known mitogen in many tissues and stimulates the growth of colorectal cancer cells in vitro [5,6]. Several studies have shown increased proliferation of the colonic epithelium in acromegaly, proportional to serum IGF-1 levels [7,8].…”

Insulin-like growth factor binding protein-3 enhances etoposide-induced cell growth inhibition by suppressing the NF-κB activity in gastric cancer cells

“…The pathogenesis of gastric cancer is complex and it involves multiple factors [16]. It has been reported that gastric cancer tissues and cell lines express IGF-I, IGF-II, and some IGFBPs, including IGFBP-3, and IGF-I promotes the growth of gastric cancer cells [17,18]. Herein, we report that overexpression of IGFBP-3 enhanced cell growth inhibition induced by etoposide through suppression of the NF-jB signaling pathway in gastric cancer cells.…”