Distribution of laminin, type IV collagen and fibronectin in the invasive component of breast carcinoma

Arihiro, Koji; Inai, Kei; Kurihara, Kanji; Takeda, Shinpei; Kaneko, Mayumi

doi:10.1111/j.1440-1827.1993.tb02563.x

Cited by 3 publications

(3 citation statements)

References 24 publications

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“…Hypoxia has been shown to upregulate VEGF expression (20). Interestingly, fibronectin has been shown to be highly expressed in several tumors (27)(28)(29)(30). In addition, hypoxic conditions have been shown to stabilize fibronectin and increase its secretion from cells (26).…”

Section: Discussionmentioning

confidence: 99%

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pH Regulates Vascular Endothelial Growth Factor Binding to Fibronectin

Goerges

Nugent

2004

Journal of Biological Chemistry

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Hypoxia is one of the major signals that induces angiogenesis. Hypoxic conditions lead to reduced extracellular pH. Vascular endothelial growth factor (VEGF) binding to endothelial cells and the extracellular matrix (ECM) increases at acidic pH (7.0 -5.5). These interactions are dependent on heparan sulfate proteoglycans, but do not depend on the presence of VEGF receptors. Here we report that VEGF 165 and VEGF 121 binding to fibronectin also increased at acidic pH, and that these interactions are further enhanced by the addition of heparin. These results reveal that the accepted nonheparin-binding isoform of VEGF (VEGF 121 ) is converted into a heparin-binding growth factor under acidic conditions. Interestingly, we did not observe increased binding of VEGF to collagen type I at acidic pH in the presence or absence of heparin, indicating that this effect is not a general property of all heparin-binding ECM proteins. The high level of VEGF binding at acidic pH was also rapidly reversed as demonstrated by increased rates of VEGF dissociation from fibronectin and fibronectin-heparin matrices as the pH was raised. The VEGF released from fibronectin retained its ability to stimulate the activation of extracellular-regulated kinase 1/2 in endothelial cells. These results suggest that VEGF may be stored in the extracellular matrix via interactions with fibronectin and heparan sulfate in tissues that are in need of vascularization so that it can aid in directing the dynamic process of growth and migration of new blood vessels.

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Section: Discussionmentioning

confidence: 99%

“…Interestingly, hypoxic conditions have been shown to stabilize fibronectin and increase its secretion from cells (26). In addition, fibronectin has been associated with being highly expressed in several tumors (27)(28)(29)(30). Thus, fibronectin might participate in directing angiogenesis via pH-sensitive binding of VEGF.…”

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confidence: 99%

pH Regulates Vascular Endothelial Growth Factor Binding to Fibronectin

Goerges

Nugent

2004

Journal of Biological Chemistry

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“…We have recently demonstrated that H-Ras induces pro-MMP-2 activation in MCF10A cells when cultured in two-dimensional gel of type I collagen (Kim et al, 2007). Since fibronectin has been shown to be associated with cellular invasiveness in various cancer cells including breast carcinoma, papillary thyroid carcinoma and colon cancer cells (Arihiro et al, 1993;Ryu et al, 1999;Ito et al, 2004;Ding et al, 2008), the present study investigates the effect of fibronectin on pro-MMP-2 activation in H-Ras MCF10A cells. Here we show that fibronectin induces activation of pro-MMP-2 and invasive and migratory abilities of H-Ras MCF10A cells.…”

Section: Introductionmentioning

confidence: 99%

Fibronectin Induces Pro-MMP-2 Activation and Enhances Invasion in H-Ras-Transformed Human Breast Epithelial Cells

Kim¹,

Moon²

2009

Biomolecules and Therapeutics

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-Interactions between tumor cells and the extracellular matrix (ECM) strongly influence tumor development, affecting cell survival, proliferation and migration. Fibronectin, a major component of ECM, has been shown to interact with integrins especially the α5β1 integrin. Cell invasion and metastasis are often associated with matrix metalloproteinases (MMPs) which are capable of digesting the different components of the ECM and basement membrane. MMP-2 is produced as a latent pro-MMP-2 (72 kDa) to be activated, resulting the 62 kDa active MMP-2. In this study, we investigated the effect of fibronectin on activation of pro-MMP-2 and the cellular invasiveness in H-Ras-transformed MCF10A human breast epithelial cells. Here we show that fibronectin induces activation of pro-MMP-2 and up-regulation of MT1-MMP and TIMP-2 in H-Ras MCF10A cells. These results demonstrate that H-Ras MCF10A cells secrete high levels of active MMP-2 when cultured with fibronectin, suggesting a possible interaction between the ECM network and H-Ras MCF10A cells to generate active MMP-2 which is important for proteolysis and ECM remodeling. Invasive and migratory abilities of H-Ras MCF10A cells were enhanced by fibronectin. Fibronectin up-regulated the expression of β1 integrin which may play a role in cellular responses exerted by fibronectin. Since acquisition of pro-MMP-2 activation can be associated with increased malignant progression, this study provides a mechanism for the cell surface-matrix degrading effect of fibronectin which will be crucial to breast cell invasion and migration.

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Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors

Weidner

1995

Breast Cancer Res Tr

641

429

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Abundant evidence has shown that tumor growth and metastasis are dependent upon tumor angiogenesis (TA). TA refers to the growth of new vessels toward and within the tumor. Until TA occurs, tumors grow no larger than 2-4 mm in diameter. Also, TA is necessary at the beginning and at the end of the metastatic cascade of events. Thus, it seems reasonable that increasing intratumoral microvascular density (iMVD) might correlate with greater tumor aggressiveness, such as a higher frequency of metastases and/or decreased survival. Indeed, in 1991 my colleagues and I reported a statistically significant association between greater incidence of metastases in patients with breast carcinoma and increasing iMVD. Microvessel density was measured with a light microscope in a single area of invasive tumor (200x field or 0.74 mm2) representative of the highest microvessel density (neovascular "hot spot"). This was done after endothelial cells, lining the microvessels, had been highlighted with anti-factor VIII-related antigen/von Willebrand's factor (F8RA/vWF). Subsequent studies by other investigators, using either anti-F8RA/vWF or other relatively vessel-specific reagents such as anti-CD31, have shown that the association of greater tumor aggressiveness with increasing iMVD exists not only in breast carcinoma, but also in other solid tumors. This article reviews the methods of highlighting intratumoral vessels and describes the techniques for counting these vessels for assessing iMVD.

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Distribution of laminin, type IV collagen and fibronectin in the invasive component of breast carcinoma

Cited by 3 publications

References 24 publications

pH Regulates Vascular Endothelial Growth Factor Binding to Fibronectin

pH Regulates Vascular Endothelial Growth Factor Binding to Fibronectin

Fibronectin Induces Pro-MMP-2 Activation and Enhances Invasion in H-Ras-Transformed Human Breast Epithelial Cells

Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors

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