Pathology & Oncology Research

, Volume 7, Issue 4, pp 251–259 | Cite as

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

  • Xiaohua Qian
  • Vicki L. Rothman
  • Roberto F. Nicosia
  • George P. Tuszynski


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.


extracellular matrix thrombospondin-1 matrix metalloproteinase pancreatic cancer tumor invasion tissue inhibitor of metalloproteinase 


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Copyright information

© Arányi Lajos Foundation 2001

Authors and Affiliations

  • Xiaohua Qian
    • 2
  • Vicki L. Rothman
    • 1
  • Roberto F. Nicosia
    • 2
    • 3
  • George P. Tuszynski
    • 1
    • 2
  1. 1.Department of SurgeryMCP Hahnemann UniversityPhiladelphiaUSA
  2. 2.Department of PathologyMCP Hahnemann UniversityPhiladelphiaUSA
  3. 3.Hahnemann UniversityPhiladelphiaUSA

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