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Tissue Engineering of Tumor Stromal Microenvironment with Application to Cancer Cell Invasion
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Tissue Engineering of Tumor Stromal Microenvironment with Application to Cancer Cell Invasion

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Stromal cells as the major source for matrix metalloproteinase-2 in cutaneous melanoma

Uta B Hofmann1, Andreas A O Eggert, Katharina Blass

  • 1Department of Dermatology, Julius Maximilians University, Josef-Schneider-Street 2, 97080 Würzburg, Germany. hofmann_u1@klinik.uni-wuerzburg.de

Archives of Dermatological Research
|July 28, 2005
PubMed

Insights

Stromal cells are the primary source of matrix metalloproteinase-2 (MMP-2) in B16-melanoma tumors, particularly at the invasive front. However, MMP-2 expression by stromal cells depends on the tumor microenvironment.

Area of Science:

  • Oncology
  • Cancer Biology
  • Protease Function

Background:

  • Matrix metalloproteinases (MMPs) play a critical role in tumor progression, invasion, and metastasis.
  • MMP expression is observed in both tumor and stromal cells, with immunohistochemistry suggesting stromal cells as a major source.
  • Understanding the cellular source of MMPs is crucial for developing targeted cancer therapies.

Purpose of the Study:

  • To investigate the cellular origin of MMP-2 in a syngeneic B16-melanoma tumor model.
  • To determine the role of the tumor microenvironment in regulating stromal cell MMP expression.
  • To analyze MMP secretion and expression profiles of B16-melanoma cells in vitro and in vivo.

Main Methods:

  • Establishment of a slowly growing, syngeneic B16-melanoma (B78D14) tumor model.
  • In vitro analysis of MMP secretion and cell surface protein expression by B78D14 cells.
  • Subcutaneous tumor implantation and analysis using immunohistochemistry and in situ zymography.
  • Experimental pulmonary metastasis model to assess MMP-2 expression in different microenvironments.

Main Results:

  • B16-melanoma cells secreted MMP-2, MT1-MMP, and MMP-9 in vitro and expressed MT1-MMP and EMMPRIN on their surface.
  • In subcutaneous tumors, MMP-2 expression was concentrated at the tumor-stroma border, indicating stromal cells as the primary in vivo source.
  • Double staining and in situ zymography confirmed MMP-2 expression and activation in tumor-adjacent stromal cells at the invasive front.
  • Neither tumor nor stromal cells expressed MMP-2 in an experimental pulmonary metastasis model.

Conclusions:

  • Stromal cells are the predominant source of MMP-2 in B16-melanoma tumors, particularly at the invasive front.
  • The expression and activation of MMP-2 by stromal cells are highly dependent on the tumor microenvironment.
  • These findings highlight the importance of the tumor microenvironment in regulating protease activity during cancer progression.

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