Integrin α 6 β 1 plays a significant role in the attachment of hepatoma cells to laminin

Torimura, Takuji; Ueno, Takato; Kin, Motoaki; Ogata, Riko; Inuzuka, Sadataka; Sugawara, Hiroshi; Kurotatsu, Ryoko; Shimada, Masahiro; Yano, Hirohisa; Kojiro, Masamichi; Tanikawa, Kyuichi; Sata, Michio

doi:10.1016/s0168-8278(99)80355-9

Cited by 31 publications

(18 citation statements)

References 28 publications

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“…In HCC, overexpression of integrins, including β1-integrin has been shown, [18][19][20] and several in vitro studies have demonstrated that the levels of constitutive activity of β1-integrins are correlated with invasive and metastatic activity of hepatoma cells. [37][38][39] Pollman et al 40) reported that ECM protected vascular endothelial cells from TGF-β1-induced apoptosis, and this anti-apoptotic effect of ECM was mimicked by activation of β1-integrin. Consistent with this observation, we have demonstrated that β1-integrin protects hepatoma cells from chemotherapy-induced apoptosis, 23) indicating that β1-integrin functions as a survival factor in hepatoma cells.…”

Section: Discussionmentioning

confidence: 99%

Transforming growth factor‐β1‐induced apoptosis is blocked by β1‐integrin‐mediated mitogen‐activated protein kinase activation in human hepatoma cells

Zhang¹,

Ozaki²,

Mizuta³

et al. 2004

Cancer Science

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Growth factors and extracellular matrices cooperatively regulate cellular behavior. However, the interactions between transforming growth factor‐β1 (TGF‐β1) and integrins in hepatic cells are not fully understood. We investigated the effects of β1‐integrin on TGF‐β1‐regulated growth of hepatoma cells. Human hepatoma cell lines HepG2, Huh7, and Hep3B were stably transfected with β1‐integrin, and the parental, and mock‐ and β1‐integrin‐transfected hepatoma cells were treated with TGF‐β1. Modulation of apoptosis and pathways involved in the process were investigated. TGF‐β1 suppressed the growth of hepatoma cells, and apoptosis was observed in Hep3B and Huh7. Hepatoma cells transfected with β1‐integrin were protected from TGF‐β1‐induced apoptosis. Mitogen‐activated protein (MAP) kinase inhibitors, PD98059, SB203580, and SP600125, abolished this protective effect of β1‐integrin, but herbimycin A and wortmannin were ineffective. Hepatoma cells overexpressing β1‐integrin showed increased activities of MAP kinases, and TGF‐β1 induced sustained activation of MAP kinases in these cells, but only transient activation in mock‐transfected cells. These data suggest that MAP kinases activated by β1‐integrin provide a strong anti‐apoptotic signal during TGF‐β1‐induced apoptosis in human hepatoma cells. Therefore β1‐integrin‐mediated signals may contribute to the development and progression of hepatocellular carcinoma.

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Section: Discussionmentioning

confidence: 99%

Transforming growth factor‐β1‐induced apoptosis is blocked by β1‐integrin‐mediated mitogen‐activated protein kinase activation in human hepatoma cells

Zhang¹,

Ozaki²,

Mizuta³

et al. 2004

Cancer Science

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“…From our results, this antibody dramatically impaired cell spreading on LN-1 and modulated cell survival, proliferation and steroidogenesis of GC cultured on LN-1. Accordingly, the GoH3 antibody has been shown to inhibit adhesion of pancreatic carcinoma cells (Vogelmann et al 1999) and hepatoma cells (Torimura et al 1999), and to impair migration of gingival epithelial cells (Gräber et al 1999) and hepatocarcinoma cells (Nejjari et al 1999) cultured on a LN substratum. In ovine GC, no effect of this antibody was observed when cells were cultured on non-coated substratum, RGD peptides, or heat-denatured LN, indicating that all the observed effects on ovine GC were specific of an interaction between 6 1 and structurally intact LN.…”

Section: Discussionmentioning

confidence: 99%

Laminin-alpha6beta1 integrin interaction enhances survival and proliferation and modulates steroidogenesis of ovine granulosa cells

Bellego¹,

Pisselet²,

Huet³

et al. 2002

Journal of Endocrinology

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This study aimed to determine the physiological role of laminin (LN) and its receptor, 6 1 integrin, in controlling the functions of granulosa cells (GC) during follicular development in sheep ovary. Immunohistochemistry experiments showed the presence of increasing levels of LN (P<0·0001), and high levels of mature 6 1 integrin in GC layers of healthy antral follicles during the follicular and the preovulatory phases of the estrous cycle. In vitro, the addition of a function-blocking antibody raised against 6 subunit (anti-6 IgG) to the medium of ovine GC cultured on LN impaired cell spreading (P<0·0001), decreased the proliferation rate (P<0·05) and increased the apoptosis rate (P<0·05). Furthermore, addition of anti-6 IgG enhanced estradiol (E2) secretion by GC in the presence or absence of follicle-stimulating hormone (FSH), luteinizing hormone or insulin-like growth factor-I in culture medium (P<0·0001), and inhibited progesterone (P4) secretion in basal conditions or in the presence of low (0·5 ng/ml) FSH concentrations only (P<0·0001). The anti-6 IgG effect was specific to an interaction of LN with 6 1 integrin since it was ineffective on GC cultured on heat-denatured LN, RGD (arginine-glycine-aspartic acid) peptides and non-coated substratum. Hence, this study established that 6 1 integrin 1) was expressed in GC of antral follicles, 2) mediated the actions of LN on survival, proliferation and steroidogenesis of GC, and 3) was able to dramatically modulate P4 and E2 secretion by GC in vitro. It is suggested that during the follicular and the preovulatory phases of the estrous cycle, the increasing levels of LN in GC of large antral follicles might support their final development to ovulation.

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“…Integrins are characterized as a family of cell surface receptors for extracellular matrix proteins such as laminin [50]. 3, 6, 1, 4 integrin subunits examined in this study are expressed in various epithelial cells and are concerned with tumor invasion or metastasis [8,19,33,49]. Northern and Western blotting analysis suggested that mRNA and proteins of 6, 1 and 4 integrins were heterogeneously expressed in DMBA-induced mammary tumors and a cell line derived from this tumor [22].…”

Section: Introductionmentioning

confidence: 72%

Characteristic Patterns of VEGF, Integrins, ER.ALPHA. and HER2 Immunoreactivity Suggest Two Tumor Cell Populations in DMBA-Induced Rat Mammary Tumor

Inoue

Kaidoh

Inoué

et al. 2005

Acta Histochem. Cytochem

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Integrin α 6 β 1 plays a significant role in the attachment of hepatoma cells to laminin

Cited by 31 publications

References 28 publications

Transforming growth factor‐β1‐induced apoptosis is blocked by β1‐integrin‐mediated mitogen‐activated protein kinase activation in human hepatoma cells

Transforming growth factor‐β1‐induced apoptosis is blocked by β1‐integrin‐mediated mitogen‐activated protein kinase activation in human hepatoma cells

Laminin-alpha6beta1 integrin interaction enhances survival and proliferation and modulates steroidogenesis of ovine granulosa cells

Characteristic Patterns of VEGF, Integrins, ER.ALPHA. and HER2 Immunoreactivity Suggest Two Tumor Cell Populations in DMBA-Induced Rat Mammary Tumor

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