Novel function for beta 1 integrins in keratinocyte cell-cell interactions.

Abstract

Abstract. We have examined the expression, localization, and function of/$~ integrins on cultured human epidermal keratinocytes using polyclonal and monoclonal antibodies against the/~,, 0~2, 0~3, and 0~5 integrin subunits. The/3, polypeptide, common to all class 1 integrins, was localized primarily in areas of cell-cell contacts of cultured keratinocytes, as were or2 and t~3 polypeptides, suggesting a possible role in cell-cell adhesion for these integrin polypeptides. In contrast, the fibronectin receptor or5 subunit showed no such accumulations in regions of cell-ceU contact but was more diffusely distributed in the keratinocyte plasma membrane, consistent with the absence of fibronectin at cell-cell contact sites. Colonies of cultured keratinocytes could be dissociated by treatment with monoclonal antibody specific to the ~1 polypeptide. Such dissociation of cell-cell contacts also occurred under conditions where the monoclonal antibody had no effect on cell-substrate adhesion. Therefore,/3~ integrin-dependent cell-cell adhesion can be inhibited without affecting other cell-adhesive interactions. Antibody treatment of keratinocytes maintained in either low (0.15 mM) or high (1.2 mM) CaC12 also resulted in the loss of organization of intracellular F-actin illaments and ~ integrins, even when the anti-~t monoclonal antibody had no dissociating effect on keratinocyte colonies at the higher calcium concentration. Our results indicate that B~ integrins play roles in the maintenance of cell-cell contacts between keratinocytes and in the organization of intracellular microfilaments. They suggest that in epithelial cells integrins can function in cell-cell interactions as well as in cellsubstrate adhesion.

Morphoregulatory activities of E-cadherin and beta-1 integrins in colorectal tumour cells

“…(Larjava et al, 1990;Benchimol et al, 1989). These results are in agreement with previous reports showing that as long as cadherins are functioning, the inactivation of other adhesion systems has little effect on cell-cell adhesion (Duband et al, 1987).…”

“…In addition some P1 integrins (@2P1 and ay P1) have been shown to function as intercellular adhesion molecules in keratinocytes growing in culture medium with low calcium concentration (Larjava et al, 1990;Carter et al, 1991).…”

β1 integrin–extracellular matrix interactions are essential for maintaining exocrine pancreas architecture and function

“…28 This study also showed decreased focal adhesion contacts in b1 integrindeficient mammary epithelium when compared with controls. 27 Taken together, the findings of this study demonstrate that reduced b1 integrin in PSCs had a direct effect on ECM expression, which in turn effected acinar cell b1 integrin expression, cell-cell interactions, and subsequently cell proliferation and death.…”

“…26 Ablation of b1 integrin by inactivating monoclonal antibody treatment disrupted cellcell contacts of keratinocytes. 27 Likewise, mouse mammary gland alveoli deficient of b1 integrin could not attach to the basement membrane laminin substratum. 28 This study also showed decreased focal adhesion contacts in b1 integrindeficient mammary epithelium when compared with controls.…”

Soluble E-cadherin fragments increased in circulation of cancer patients

“…The biological potency of soluble E-cadherin released from cultured cells has already been characterised in in vitro experiments (Wheelock et al, 1987). Some PI-integrins have been shown to function as intercellular adhesion molecules in in vitro cultured keratinocytes (Larjava et al, 1990), and therefore the function or in vivo localisation of integrin P in tumour cells is often compared with that of cadherins using immunological analysis (Pignatelli et al, 1992). Many reports have suggested, contrary to the findings for E-cadherin, that the surface expression of integrin PI is uniformly elevated in metastatic tumour cells and potentially mediates the tight adhesion of these cells to the subendothelial matrix substratum (Feldman et al, 1991;Martin-Padura et al, 1991).…”