Distribution of Extracellular Matrix Proteins in Pancreatic Ductal Adenocarcinoma and Its Influence on Tumor Cell Proliferation in Vitro

Mollenhauer, Jürgen; Roether, I; Kern, Horst F.

doi:10.1097/00006676-198701000-00003

Cited by 127 publications

(89 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While expression of the a 2 integrin subunit has been demonstrated previously for most of these cell lines (Lohr et al, 1996;Sawai et al, 2001;Miyamoto et al, 2004), to our knowledge, this is the first demonstration that the CFPAC cell line is also a 2 integrin subunit positive. These results are in agreement with reports using other pancreatic cancer cell lines, including PC-2, -3, and -44, PaTu 8988S, HPAF, Capan-2, PaTu 8902, and PaTu-2 cells, which also demonstrated type I collagen adhesion and a 2 integrin subunit expression (Mollenhauer et al, 1987;Weinel et al, 1992). Control Anti-1 Anti-2 Anti-3 Anti-1 Figure 5 The a 2 b 1 integrin mediates pancreatic cancer cell adhesion and haptokinetic migration on type I collagen.…”

Section: Discussionsupporting

confidence: 93%

“…The clear indication that most of our pancreatic cancer cell lines attach, proliferate, and migrate maximally on type I collagen compared to the other ECM proteins examined is not surprising, in that the hallmark desmoplastic reaction associated with pancreatic adenocarcinoma, including upregulated type I collagen expression, has been appreciated for some time now (Mollenhauer et al, 1987;Lohr et al, 1994;Shimoyama et al, 1995;Tani et al, 1997;Kuehn et al, 1999;Linder et al, 2001;Tempia-Caliera et al, 2002). Recent analyses using microarray and serial analysis of gene expression technology confirm those studies and point out the strong expression of many other ECM genes in pancreatic cancer as well (Iacobuzio-Donahue et al, 2003a, b;Binkley et al, 2004;Stein et al, 2004).…”

Section: Discussionmentioning

confidence: 82%

“…The previous demonstrations that type I collagen is clearly upregulated (Mollenhauer et al, 1987;Lohr et al, 1994;Shimoyama et al, 1995;Tani et al, 1997;Kuehn et al, 1999;Linder et al, 2001;Tempia-Caliera et al, 2002;Iacobuzio-Donahue et al, 2003a, b;Binkley et al, 2004;Stein et al, 2004), and mediates a malignant phenotype in pancreatic cancer in vivo (Armstrong et al, 2004;Bachem et al, 2005), correlates directly with our present in vitro observations, and are further extended by our demonstration that the a 2 b 1 integrin specifically regulates this type I collagen-mediated phenotype in multiple pancreatic cancer cell lines. These observations collectively suggest that targeting the a 2 b 1 integrin may have therapeutic value in the treatment of pancreatic cancer in vivo.…”

Section: Discussionmentioning

confidence: 92%

“…The SMAD4 mutations, in particular, which result in the constitutive activation of transforming growth factor b 1 (TGFb 1 ) signalling, are generally considered to be responsible for the hallmark desmoplastic response, which includes upregulated expression of the extracellular matrix (ECM), and type I collagen in particular (Mollenhauer et al, 1987;Lohr et al, 1994;Shimoyama et al, 1995;Linder et al, 2001;Bardeesy and DePinho, 2002;Menke and Adler, 2002;Tempia-Caliera et al, 2002;Iacobuzio-Donahue et al, 2003a, b).…”

mentioning

confidence: 99%

See 3 more Smart Citations

The α2β1 integrin mediates the malignant phenotype on type I collagen in pancreatic cancer cell lines

2006

View full text Add to dashboard Cite

Pancreatic cancer is characterised by a hallmark desmoplastic response that includes upregulated expression of the extracellular matrix, and type I collagen in particular. Recent studies indicate that pancreatic cancer cells stimulate type I collagen synthesis in adjacent stellate cells, and that this upregulated type I collagen expression promotes the malignant phenotype in tumour cells as defined by increased proliferation, resistance to chemically induced apoptosis, and increased tumorigenesis. The integrin specificity of this interaction between type I collagen and tumour cells was not identified, however. In the present study, we examined eight pancreatic cancer cell lines for adhesion, proliferation, and migration, on types I and IV collagen, fibronectin, laminin, and vitronectin, as well as integrin expression. Our results indicate, for the overwhelming majority of cell lines, that type I collagen promotes the strongest adhesion, proliferation, and migration relative to the other substrates tested. Utilising function-blocking monoclonal antibodies directed against particular integrin subunits in cell adhesion and migration inhibition assays, we demonstrate further that the malignant phenotype on type I collagen is mediated specifically by the a 2 b 1 integrin. These results identify a 2 b 1 integrin-mediated adhesion to type I collagen as a potential therapeutic target in the treatment of pancreatic cancer.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 92%

mentioning

confidence: 99%

See 2 more Smart Citations

The α2β1 integrin mediates the malignant phenotype on type I collagen in pancreatic cancer cell lines

2006

View full text Add to dashboard Cite

show abstract

“…Pancreatic carcinomas produce high amounts of extracellular matrix (ECM) consisting mainly of fibronectin, collagen type I and collagen type V (Mollenhauer et al, 1987). The microenvironment influences cell differentiation and behaviour and is considered as an important factor in cancer progression (reviewed by Erickson and Barcellos-Hoff, 2003).…”

mentioning

confidence: 99%

Collagen type I-induced Smad-interacting protein 1 expression downregulates E-cadherin in pancreatic cancer

et al. 2006

View full text Add to dashboard Cite

Pancreatic cancer is a devastating disease with poor prognosis. Production of large quantities of extracellular matrix and early metastasis are characteristics of this disease. One important step in the development of various cancers is the loss of E-cadherin gene expression or inactivation of E-cadherin mediated cell-cell adhesion. It has been shown that collagen type I promotes downregulation of E-cadherin expression, which correlates with enhanced cell migration and invasiveness. In this context, we elucidated the role of Smad-interacting protein 1 (SIP1), which has been discussed as a negative regulator of E-cadherin gene expression. We demonstrate that SIP1 upregulation shows an inverse relationship with E-cadherin in advanced pancreatic tumour stages. In Panc-1 cells, SIP1 expression can be induced by exposure to collagen type I in a src-dependent manner. In addition, overexpression of SIP1 reduces E-cadherin mRNA and protein levels. Taken together, these results suggest that SIP1 is involved in the progression of pancreatic cancer and plays a role in mediating signal transduction from collagen type I to downregulate E-cadherin expression.

show abstract

Imbalance of expression of matrix metalloproteinases (MMPs) and tissue inhibitors of the matrix metalloproteinases (TIMPs) in human pancreatic carcinoma

et al. 1997

View full text Add to dashboard Cite

Degradation of the extracellular matrix (ECM) is an essential step in tumour invasion and metastasis. The matrix metalloproteinases (MMPs) each have different substrate specificities within the ECM and are important in its degradation. MMP activity is dependent on the levels of activated MMP and tissue inhibitors of matrix metalloproteinases (TIMPs). The expression of MMPs and TIMPs in pancreatic carcinoma, normal pancreas, and pancreatic carcinoma cell lines has been determined by Northern analysis. The transcripts have been localized by in situ hybridization and the MMP2 protein by immunohistochemistry. Expression of MMP2, ‐7, and ‐11 was greater in pancreatic carcinoma than in normal pancreas (P<0·01). MMP7 expression in normal pancreas and MMP7 and ‐11 expression in tumours was always seen with TIMP1 expression. TIMP2 was expressed in only half of the tumours and a previously undescribed transcript size is reported for TIMP2. MTMMP was expressed concurrently with MMP2 in 64 per cent of tumours, but concurrent MMP2 and TIMP2 expression occurred in only half. MMP2 mRNA was found more often in the tumour stroma than with the other MMPs or TIMPs (P<0·02). It is concluded that while overexpression of MMP7 and ‐11 may be countered by TIMP1, the aggressive phenotype of pancreatic carcinoma may occur because of overexpression of MMP2, activated by MTMMP and associated with a reduced expression of TIMP2. © 1997 John Wiley & Sons, Ltd.

show abstract

Distribution of Extracellular Matrix Proteins in Pancreatic Ductal Adenocarcinoma and Its Influence on Tumor Cell Proliferation in Vitro

Cited by 127 publications

References 0 publications

The α2β1 integrin mediates the malignant phenotype on type I collagen in pancreatic cancer cell lines

The α2β1 integrin mediates the malignant phenotype on type I collagen in pancreatic cancer cell lines

Collagen type I-induced Smad-interacting protein 1 expression downregulates E-cadherin in pancreatic cancer

Imbalance of expression of matrix metalloproteinases (MMPs) and tissue inhibitors of the matrix metalloproteinases (TIMPs) in human pancreatic carcinoma

Contact Info

Product

Resources

About