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Expression of thrombospondin-1 in human pancreatic adenocarcinomas: Role in matrix metalloproteinase-9 production

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Pathology & Oncology Research

Abstract

Human pancreatic adenocarcinoma, an aggressive malignant disease, shows a strong desmoplastic reaction characterized by a remarkable proliferation of interstitial connective tissues. Thrombospondin-1 (TSP-1), a 450 kDa platelet and matrix glycoprotein, has been implicated in tumor invasion, angiogenesis and metastasis. TSP-1 and MMP-9 expression in pancreatic adenocarcinoma and control pancreas tissues was measured by immunohistochemistry. TSP-1 expression in pancreatic carcinoma cell lines, fibroblasts, and endothelial cells was measured by a competitive TSP-1 enzyme linked immunosorbent assay (ELISA). The effect of TSP-1 on MMP-9 production in pancreatic carcinoma cell lines was measured by zymography and Western blot analysis. Eighty five per cent (23/27) of cases of pancreatic adenocarcinoma showed increased TSP-1 staining in the desmoplastic stroma adjacent to tumor cells. No specific positive staining for TSP-1 was observed in the normal pancreatic tissues and the inflammatory areas. TSP-1 localized in tumor stroma surrounding the tumor cells expressing MMP-9. Using TSP-1 competitive ELISA, the secretion of TSP-1 by different pancreatic cancer cell lines into culture medium varied from 11.45 ±14.08 to 275.82 ±45.56 ng/106 cells/24 hours. The amounts of TSP-1 detected in both culture media and cell extracts from fibroblasts or endothelial cells were at least 2–3 fold higher than those from pancreatic cancer cells. TSP-1 augmented the production of matrix metalloproteinase-9, a matrix degrading enzyme, in pancreatic cancer cellsin vitro. Stromally-derived TSP-1 up-regulates the production of MMP-9 by pancreatic adenocarcinoma. These data are consistent with the conclusion that TSP-1-rich stroma is involved in regulating matrix remodeling in tumor invasion.

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Authors and Affiliations

  1. Department of Surgery, MCP Hahnemann University, Philadelphia, Pennsylvania, USA

    Vicki L. Rothman & George P. Tuszynski

  2. Department of Pathology, MCP Hahnemann University, Philadelphia, Pennsylvania, USA

    Xiaohua Qian, Roberto F. Nicosia & George P. Tuszynski

  3. Hahnemann University, Broad and Vine Streets, 19102-1192, Philadelphia, PA, USA

    Roberto F. Nicosia

Authors
  1. Xiaohua Qian
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  2. Vicki L. Rothman
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  3. Roberto F. Nicosia
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  4. George P. Tuszynski
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Corresponding author

Correspondence to George P. Tuszynski.

Additional information

Supported in part by a grant 1 R01 CA88931 to GPT and HL52585 to RFN from the National Institutes of Health.

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Qian, X., Rothman, V.L., Nicosia, R.F. et al. Expression of thrombospondin-1 in human pancreatic adenocarcinomas: Role in matrix metalloproteinase-9 production. Pathol. Oncol. Res. 7, 251–259 (2001). https://doi.org/10.1007/BF03032381

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  • DOI: https://doi.org/10.1007/BF03032381

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