Regulation of fibronectin and laminin receptor expression, fibronectin and laminin secretion in human colon cancer cells by transforming growth factor‐β₁

Abstract

Transforming growth factor (TGF)-beta 1 modulates the expression of extracellular matrix (ECM) glycoproteins, fibronectin and laminin and the adhesion of Moser colon cancer cells to these glycoproteins. Since adhesion can be altered through expression of cell-surface receptors, binding affinities of adhesion molecules for receptors, or both, we investigated the effect of TGF-beta 1 on the binding properties of fibronectin and laminin to their cell-surface receptors by saturation binding and Scatchard analyses using radiolabeled fibronectin and laminin. Fibronectin bound to its cell-surface receptor with high affinity (Kd = 1.25 x 10(-9) M), Moser cells had approximately 7.1 x 10(4) fibronectin-binding sites per cell. TGF-beta 1 treatment rapidly up-modulated the number of cell-surface fibronectin-binding sites by 1.9-fold. The binding affinity of fibronectin for the receptor, however, was not altered. Laminin was found to bind to a higher-affinity and a lower-affinity receptor. Moser cells expressed approximately 1.1 x 10(3) higher-affinity laminin-binding sites and approximately 3.1 x 10(4) lower-affinity-binding sites per cell. TGF-beta 1 rapidly increased the expression of the higher-affinity sites 3-fold and the lower-affinity sites 5-fold. The binding affinity of both the higher-affinity and lower-affinity laminin receptors increased 3-fold after 2 and 6 hr of TGF-beta 1 treatment respectively. Concurrent with receptor modulation, TGF-beta 1 induced the secretion of fibronectin and laminin from Moser cells. Northern hybridization analyses showed a concurrent stimulation of the expression of the mRNAs for ligands (fibronectin and laminin) and the mRNAs for the integrin species of the fibronectin and laminin receptors (alpha 5 and alpha 6 subunits). Thus the production of fibronectin and laminin and the expression of their receptors were tightly co-regulated by TGF-beta 1.

Proinflammatory cytokines TNF-α and IFN-γ alter laminin expression under an apoptosis-independent mechanism in human intestinal epithelial cells

“…To validate the dot blot immunoassay, HIEC were treated with TGF-␤ (1-10 ng/ml) under serum-free conditions for 72 h. It is known that TGF-␤1 promotes the secretion of extracellular matrix proteins such as laminin in rat and human cell lines (27,30). In our hands, TGF-␤ increases the expression of the two laminins produced by epithelial cells in a dose-dependent manner (Fig.…”

Functional Genomic Analysis Reveals Cross-talk between Peroxisome Proliferator-activated Receptor γ and Calcium Signaling in Human Colorectal Cancer Cells

“…The MOSER S line that we have used in these experiments is sensitive to TGF␤ (54,78). TGF␤ sensitivity is generally lost in colorectal cancer cells during the transition from adenoma to adenocarcinoma, suggesting that MOSER cells represent a very early adenocarcinoma or late adenoma stage in colon cancer development.…”

“…The observations described below result from such a study in which we used the high affinity PPAR␥ agonist RS5444 (14,(51)(52)(53) to activate PPAR␥ in MOSER cells. These cells have sustained an APC loss-of-function mutation followed by loss of heterozygosity of the wildtype APC allele; however, MOSER cells retain TGF␤ sensitivity (54,55) and have wild-type K-Ras, indicating that they represent a late adenoma or early adenocarcinoma stage. Furthermore, PPAR␥ inhibits transformed properties of MOSER cells (56), making them an ideal model to study the mechanism whereby this receptor inhibits early steps in transformation of colonic epithelial cells.…”

Study of in vitro and in vivo effects of 1,6-Bis[4-(4-amino-3-hydroxyphenoxy)phenyl]diamantane (DPD), a novel cytostatic and differentiation inducing agent, on human colon cancer cells

“…The morphology of HT-29 cells can be modulated to express distinct differentiation markers following treatment with various inducers (Fantini et al, 1990;Cohen et al, 1999). The induction of differentiation in human colon cancer cells is associated with an upregulation of production of the differentiation-related molecules fibronectin (FN) and carcinoembryonic antigen (CEA) (Drewinko et al, 1976;Brattain et al, 1984;Huang and Chakrabarty, 1994).…”