The α3β1 integrin is associated with mammary carcinoma cell metastasis, invasion, and gelatinase B (mmp-9) activity

Morini, Monica; Mottolese, Marcella; Ferrari, Nicoletta; Ghiorzo, Federica; Buglioni, Simonetta; Mortarini, Roberta; Noonan, Douglas M.; Natali, Pier Giorgio; Albini, Adriana

doi:10.1002/1097-0215(20000801)87:3<336::aid-ijc5>3.0.co;2-3

Cited by 249 publications

(195 citation statements)

References 23 publications

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“…Our results also demonstrated that SAHA and TRAIL either alone or in combination were unable to exert any effect on the levels of a5 and b1 integrin subunits, which have been reported to be up-regulated in MDA-MB231 cells and seem to be involved in the survival and migration of these cells [31,32]. However, we cannot exclude that SAHA/TRAIL co-treatment modified the levels of other integrin subunits, since aberrant expression of several other integrins has been shown in breast cancer cell lines [52,53].…”

Section: Discussionmentioning

confidence: 47%

SAHA/TRAIL combination induces detachment and anoikis of MDA-MB231 and MCF-7 breast cancer cells

et al. 2012

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a b s t r a c t SAHA, an inhibitor of histone deacetylase activity, has been shown to sensitize tumor cells to apoptosis induced by TRAIL, a member of TNF-family. In this paper we investigated the effect of SAHA/TRAIL combination in two breast cancer cell lines, the ERaÀpositive MCF-7 and the ERaÀnegative MDA-MB231. Treatment of MDA-MB231 and MCF-7 cells with SAHA in combination with TRAIL caused detachment of cells followed by anoikis, a form of apoptosis which occurs after cell detachment, while treatment with SAHA or TRAIL alone did not produce these effects. The effects were more evident in MDA-MB231 cells, which were chosen for ascertaining the mechanism of SAHA/TRAIL action. Our results show that SAHA decreased the level of c-FLIP, thus favouring the interaction of TRAIL with the specific death receptors DR4 and DR5 and the consequent activation of caspase-8. These effects increased when the cells were treated with SAHA/TRAIL combination. Because z-IEDT-fmk, an inhibitor of caspase-8, prevented both the cleavage of the focal adhesion-kinase FAK and cell detachment, we suggest that activation of caspase-8 can be responsible for both the decrement of FAK and the consequent cell detachment. In addition, treatment with SAHA/TRAIL combination caused dissipation of DJ m , activation of caspase-3 and decrement of both phospho-EGFR and phospho-ERK1/2, a kinase which is involved in the phosphorylation of BimEL. Therefore, co-treatment also induced decrement of phospho-BimEL and a concomitant increase in the dephosphorylated form of BimEL, which plays an important role in the induction of anoikis.Our findings suggest the potential application of SAHA in combination with TRAIL in clinical trials for breast cancer.

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Section: Discussionmentioning

confidence: 47%

SAHA/TRAIL combination induces detachment and anoikis of MDA-MB231 and MCF-7 breast cancer cells

et al. 2012

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“…Activated α V β 3 functionally co-operates with MMP-9, because MMP-9 stimulates α V β 3 -dependent migration of breast cancer cells (Rolli et al, 2003). Similarly, cooperation of α 3 β 1 integrin and MMP-9 in tumor invasion has been observed (Morini et al, 2000). MMP-9 also cooperates with α V β 5 integrin.…”

Section: Cell Surface Associations Of the Gelatinasesmentioning

confidence: 91%

Gelatinase-mediated migration and invasion of cancer cells

Björklund

Koivunen

2005

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

456

609

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“…A role for ␣3␤1 integrin in modulating proteolytic activity has been proposed, although this is somewhat controversial. In rhabdomyosarcoma and glioblastoma tumors, anti-␣3␤1 blocking antibody stimulates cell invasion and MMP-2 secretion, whereas in breast cancer it inhibits cell invasion and MMP-9 secretion (Chintala et al, 1996;Kubota et al, 1997;Morini et al, 2000). Furthermore, in melanoma cells the same antibody also inhibits cell migration and invasion, and in immortalized keratinocytes a deficiency of ␣3␤1 integrin suppresses MMP-9 expression.…”

Section: Giannelli Et Almentioning

confidence: 99%

Human Hepatocellular Carcinoma (HCC) Cells Require Both α3β1 Integrin and Matrix Metalloproteinases Activity for Migration and Invasion

Giannelli

Bergamini

Fransvea

et al. 2001

Laboratory Investigation

133

134

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SUMMARY:Hepatocellular carcinoma (HCC) is the most frequent malignant tumor of the liver; prognosis depends on the tendency to metastasize. Cancer cell invasion is regulated by proteolytic remodeling of extracellular matrix components and by integrin expression. We have shown that matrix metalloproteinase-2 (MMP-2) and membrane-type-1 matrix metalloproteinase (MT1-MMP) cleave Laminin-5 (Ln-5), stimulating cell migration. Here we report that all HCC cells express MT1-MMP, migrate on Ln-1 and Collagen IV, whereas only HCC cells that express ␣3␤1 integrin secrete detectable levels of gelatinases, migrate on Ln-5, and invade through a reconstituted basement membrane (BM). Migration on Ln-5 is blocked by BB-94, an MMP inhibitor, and by MIG1, a monoclonal antibody that hinders migration on MMP-2-cleaved Ln-5. Invasion through a reconstituted BM is also inhibited by BB-94. HCC ␣3␤1-negative cells migrate on Ln-1 and Collagen IV, but not on Ln-5, and do not invade through a reconstituted BM, although they express MT1-MMP. Anti-␣3␤1 blocking antibodies inhibit gelatinase activation, cell motility, and cell invasion through Matrigel. In vivo, ␣3␤1 integrin and Ln-5 are expressed in HCC tissue but not in normal liver. In conclusion, our data suggest that both ␣3␤1 integrin and gelatinase activity are required for HCC migration and invasion. (Lab Invest 2001, 81:613-627).

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The α3β1 integrin is associated with mammary carcinoma cell metastasis, invasion, and gelatinase B (mmp-9) activity

Cited by 249 publications

References 23 publications

SAHA/TRAIL combination induces detachment and anoikis of MDA-MB231 and MCF-7 breast cancer cells

SAHA/TRAIL combination induces detachment and anoikis of MDA-MB231 and MCF-7 breast cancer cells

Gelatinase-mediated migration and invasion of cancer cells

Human Hepatocellular Carcinoma (HCC) Cells Require Both α3β1 Integrin and Matrix Metalloproteinases Activity for Migration and Invasion

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