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Cathepsin S from both tumor and tumor‐associated cells promote cancer growth and neovascularization
Author(s) -
Small Donna M.,
Burden Roberta E.,
Jaworski Jakub,
Hegarty Shauna M.,
Spence Shaun,
Burrows James F.,
McFarlane Cheryl,
Kissenpfennig Adrien,
McCarthy Helen O.,
Johnston James A.,
Walker Brian,
Scott Christopher J.
Publication year - 2013
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.28238
Subject(s) - cathepsin s , cancer research , cathepsin , tumor microenvironment , tumor progression , biology , angiogenesis , cathepsin b , cathepsin d , neovascularization , cancer , pathology , medicine , tumor cells , enzyme , biochemistry , genetics
Recent murine studies have demonstrated that tumor‐associated macrophages in the tumor microenvironment are a key source of the pro‐tumorigenic cysteine protease, cathepsin S. We now show in a syngeneic colorectal carcinoma murine model that both tumor and tumor‐associated cells contribute cathepsin S to promote neovascularization and tumor growth. Cathepsin S depleted and control colorectal MC38 tumor cell lines were propagated in both wild type C57Bl/6 and cathepsin S null mice to provide stratified depletion of the protease from either the tumor, tumor‐associated host cells, or both. Parallel analysis of these conditions showed that deletion of cathepsin S inhibited tumor growth and development, and revealed a clear contribution of both tumor and tumor‐associated cell derived cathepsin S. The most significant impact on tumor development was obtained when the protease was depleted from both sources. Further characterization revealed that the loss of cathepsin S led to impaired tumor vascularization, which was complemented by a reduction in proliferation and increased apoptosis, consistent with reduced tumor growth. Analysis of cell types showed that in addition to the tumor cells, tumor‐associated macrophages and endothelial cells can produce cathepsin S within the microenvironment. Taken together, these findings clearly highlight a manner by which tumor‐associated cells can positively contribute to developing tumors and highlight cathepsin S as a therapeutic target in cancer.