Diminished expression of integrin adhesion molecules on human colonic epithelial cells during the benign to malign tumour transformation.

Stallmach, Andreas; Lampe, B; Matthes, Harald; Bornhöft, Gudrun; Riecken, Ernst–Otto

doi:10.1136/gut.33.3.342

Cited by 136 publications

(80 citation statements)

References 27 publications

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“…However, the role of ␣5␤1 integrin in colon cancer is likely to be complex, and somewhat discordant results have been reported in the literature. In terms of the expression of ␣5␤1, one group (Stallmach et al, 1992) has reported a progressive loss of integrin expression (including ␣5␤1) with increasing neoplastic transformation, whereas another group (Gong et al, 1997) has found that highly invasive colon tumor lines express ␣5␤1 but poorly invasive lines do not. In terms of integrin function, our group (Varner et al, 1995) and another group (Stallmach et al, 1994) have found that overexpression of ␣5␤1 in HT29 colonic carcinoma cells resulted in a marked reduction in tumorigenicity.…”

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confidence: 99%

α5β1 Integrin Protects Intestinal Epithelial Cells from Apoptosis through a Phosphatidylinositol 3-Kinase and Protein Kinase B–dependent Pathway

Lee

Juliano

2000

MBoC

150

106

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Renewal of the gastrointestinal epithelium involves a coordinated process of terminal differentiation and programmed cell death. Integrins have been implicated in the control of apoptotic processes in various cell types. Here we examine the role of integrins in the regulation of apoptosis in gastrointestinal epithelial cells with the use of a rat small intestinal epithelial cell line (RIE1) as a model. Overexpression of the integrin ␣5 subunit in RIE1 cells conferred protection against several proapoptotic stimuli. In contrast, overexpression of the integrin ␣2 subunit had no effect on cell survival. The antiapoptotic effect of the ␣5 subunit was partially retained by a mutated version that had a truncation of the cytoplasmic domain. The antiapoptotic effects of the fulllength or truncated ␣5 subunit were reversed upon treatment with inhibitors of phosphatidylinositol 3-kinase (PI-3-kinase), suggesting that the ␣5␤1 integrin might interact with the PI-3-kinase/ Akt survival pathway. When cells overexpressing ␣5 were allowed to adhere to fibronectin, there was a moderate activation of protein kinase B (PKB)/Akt, whereas no such effect was seen in ␣2-overexpressing cells adhering to collagen. Furthermore, in cells overexpressing ␣5 and adhering to fibronectin, there was a dramatic enhancement of the ability of growth factors to stimulate PKB/Akt; again, this was not seen in cells overexpressing ␣2 subunit and adhering to collagen or fibronectin. Expression of a dominant negative version of PKB/Akt in RIE cells blocked to ability of ␣5 to enhance cell survival. Thus, the ␣5␤1 integrin seems to protect intestinal epithelial cells against proapoptotic stimuli by selectively enhancing the activity of the PI-3-kinase/Akt survival pathway. INTRODUCTIONIntegrin-mediated interactions with extracellular matrix components play crucial roles in many fundamental aspects of growth and differentiation (Aplin et al., 1998;Giancotti and Ruoslahti, 1999). For example, integrins are key regulators of the coordinated differentiation of many epithelial tissues. The functions of the ␤1 subfamily of integrins are particularly well understood in mammary development (Faraldo et al., 1998;Bissell et al., 1999) and in the differentiation of the epidermis (Watt, 1998;Zhu et al., 1999). However, integrins clearly play a role in other epithelia as well. The self-renewing cellular lining of the gastrointestinal tract is an interesting and important model for epithelial differentiation. Both in the small intestine and in the colon, epithelial renewal is accompanied by directed migration of differentiating cells away from the stem cell-rich crypts and ultimately results in apoptosis and shedding of terminally differentiated cells into the lumen of the gut (Stappenbeck et al., 1998;Karam, 1999). A variety of factors, including soluble hormones and cytokines, interactions with mesenchymal cells, and interactions with extracellular matrix, have been implicated in growth control mechanisms in the gastrointestinal tract (Burgess, 1998;Kedinger et al....

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confidence: 99%

α5β1 Integrin Protects Intestinal Epithelial Cells from Apoptosis through a Phosphatidylinositol 3-Kinase and Protein Kinase B–dependent Pathway

Lee

Juliano

2000

MBoC

150

106

View full text Add to dashboard Cite

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“…To confirm the association of av with different /3 subunits and to determine whether this subunit also associated with /31 on (Pignatelli et al, 1990;Stallmach et al, 1992). The effect of a3 occupancy by fibronectin on tumour cell growth is not known.…”

Section: Immunoprecipitation Analysismentioning

confidence: 99%

“…during tumour progression (Choy et al, 1990;Koretz et al, 1991;Stallmach et al, 1992;Nigam et al, 1993;Lindmark et al, 1993). A systematic study of integrin expression in normal colon, adenomas and carcinomas within the same patients has shown progressive loss of expression of 013, (which also recognises laminin and collagen) and a5#1, (which recognises fibronectin only) in the transition from adenomas to carcinomas (Pignatelli et al, 1990;Stallmach et al, 1992).…”

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confidence: 99%

“…A systematic study of integrin expression in normal colon, adenomas and carcinomas within the same patients has shown progressive loss of expression of 013, (which also recognises laminin and collagen) and a5#1, (which recognises fibronectin only) in the transition from adenomas to carcinomas (Pignatelli et al, 1990;Stallmach et al, 1992). In one report 75% of colorectal carcinomas were found to be completely negative for expression of the major VLA fibronectin receptor, CX5#I (Stallmach et al, 1992).…”

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confidence: 99%

“…Of these receptors, av1,, a003 and avB6 and perhaps (Xv#5 are capable of binding fibronectin (Hynes, 1992; Zhang Charo et al, 1990;Cheng et al, 1991;Busk et al, 1992;Weinacker et al, 1994 (Seftor et al, 1992). In contrast, the 13 subunit has either not been identified at all in normal and malignant epithelium (Stallmach et al, 1992) or found to be weakly expressed in a minority of tissue specimens (Nigam et al, 1993). On the other hand weak expression of a, has been reported for the majority of normal mucosal specimens and half of the tumours in one series of patients (Nigam et al, 1993).…”

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confidence: 99%

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