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Imbalanced matriptase pericellular proteolysis contributes to the pathogenesis of malignant B-cell lymphomas.

Publication ,  Journal Article
Chou, F-P; Chen, Y-W; Zhao, XF; Xu-Monette, ZY; Young, KH; Gartenhaus, RB; Wang, J-K; Kataoka, H; Zuo, AH; Barndt, RJ; Johnson, M; Lin, C-Y
Published in: The American journal of pathology
October 2013

Membrane-associated serine protease matriptase is widely expressed by epithelial/carcinoma cells in which its proteolytic activity is tightly controlled by the Kunitz-type protease inhibitor, hepatocyte growth factor activator inhibitor (HAI-1). We demonstrate that, although matriptase is not expressed in lymphoid hyperplasia, roughly half of the non-Hodgkin B-cell lymphomas analyzed express significant amounts of matriptase. Furthermore, a significant proportion of these tumors express matriptase in the absence of HAI-1. Aggressive Burkitt lymphoma was more likely than indolent follicular lymphoma to express matriptase alone (86% versus 36%). In the absence of significant HAI-1 expression, the lymphoma cells activate and shed active matriptase when the cells are stimulated with mildly acidic buffer or the hypoxia-mimicking agent, CoCl2. The shed active matriptase can initiate pericellular proteolytic cascades by activating urokinase-type plasminogen activator on the cell surface of monocytes, and it can activate prohepatocyte growth factor. In addition, matriptase knockdown suppressed proliferation and colony-forming ability of neoplastic B cells in culture and growth as tumor xenografts in mice. Furthermore, exogenous expression of HAI-1 significantly suppressed proliferation of neoplastic B cells. These studies suggest that dysregulated pericellular proteolysis as a result of unregulated matriptase expression with limited HAI-1 may contribute to the pathological characteristics of several human B-cell lymphomas through modulation of the tumor microenvironment and enhanced tumor growth.

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Published In

The American journal of pathology

DOI

EISSN

1525-2191

ISSN

0002-9440

Publication Date

October 2013

Volume

183

Issue

4

Start / End Page

1306 / 1317

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Urokinase-Type Plasminogen Activator
  • Serine Endopeptidases
  • Proteolysis
  • Proteinase Inhibitory Proteins, Secretory
  • Pathology
  • Mice, SCID
  • Mice
  • Lymphoma, B-Cell
  • Lymph Nodes
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Chou, F.-P., Chen, Y.-W., Zhao, X. F., Xu-Monette, Z. Y., Young, K. H., Gartenhaus, R. B., … Lin, C.-Y. (2013). Imbalanced matriptase pericellular proteolysis contributes to the pathogenesis of malignant B-cell lymphomas. The American Journal of Pathology, 183(4), 1306–1317. https://doi.org/10.1016/j.ajpath.2013.06.024
Chou, Feng-Pai, Ya-Wen Chen, Xianfeng F. Zhao, Zijun Y. Xu-Monette, Ken H. Young, Ronald B. Gartenhaus, Jehng-Kang Wang, et al. “Imbalanced matriptase pericellular proteolysis contributes to the pathogenesis of malignant B-cell lymphomas.The American Journal of Pathology 183, no. 4 (October 2013): 1306–17. https://doi.org/10.1016/j.ajpath.2013.06.024.
Chou F-P, Chen Y-W, Zhao XF, Xu-Monette ZY, Young KH, Gartenhaus RB, et al. Imbalanced matriptase pericellular proteolysis contributes to the pathogenesis of malignant B-cell lymphomas. The American journal of pathology. 2013 Oct;183(4):1306–17.
Chou, Feng-Pai, et al. “Imbalanced matriptase pericellular proteolysis contributes to the pathogenesis of malignant B-cell lymphomas.The American Journal of Pathology, vol. 183, no. 4, Oct. 2013, pp. 1306–17. Epmc, doi:10.1016/j.ajpath.2013.06.024.
Chou F-P, Chen Y-W, Zhao XF, Xu-Monette ZY, Young KH, Gartenhaus RB, Wang J-K, Kataoka H, Zuo AH, Barndt RJ, Johnson M, Lin C-Y. Imbalanced matriptase pericellular proteolysis contributes to the pathogenesis of malignant B-cell lymphomas. The American journal of pathology. 2013 Oct;183(4):1306–1317.
Journal cover image

Published In

The American journal of pathology

DOI

EISSN

1525-2191

ISSN

0002-9440

Publication Date

October 2013

Volume

183

Issue

4

Start / End Page

1306 / 1317

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • Urokinase-Type Plasminogen Activator
  • Serine Endopeptidases
  • Proteolysis
  • Proteinase Inhibitory Proteins, Secretory
  • Pathology
  • Mice, SCID
  • Mice
  • Lymphoma, B-Cell
  • Lymph Nodes