TY - JOUR
T1 - Cooperative effects of aminopeptidase N (CD13) expressed by nonmalignant and cancer cells within the tumor microenvironment
AU - Guzman-Rojas, Liliana
AU - Rangel, Roberto
AU - Salameh, Ahmad
AU - Edwards, Julianna K.
AU - Dondossola, Eleonora
AU - Kim, Yun Gon
AU - Saghatelian, Alan
AU - Giordano, Ricardo J.
AU - Kolonin, Mikhail G.
AU - Staquicini, Fernanda I.
AU - Koivunen, Erkki
AU - Sidman, Richard L.
AU - Arap, Wadih
AU - Pasqualini, Renata
PY - 2012/1/31
Y1 - 2012/1/31
N2 - Processes that promote cancer progression such as angiogenesis require a functional interplay between malignant and nonmalignant cells in the tumor microenvironment. The metalloprotease aminopeptidase N (APN; CD13) is often overexpressed in tumor cells and has been implicated in angiogenesis and cancer progression. Our previous studies of APN-null mice revealed impaired neoangiogenesis in model systems without cancer cells and suggested the hypothesis that APN expressed by nonmalignant cells might promote tumor growth. We tested this hypothesis by comparing the effects of APN deficiency in allografted malignant (tumor) and nonmalignant (host) cells on tumor growth and metastasis in APNnull mice. In two independent tumor graft models, APN activity in both the tumors and the host cells cooperate to promote tumor vascularization and growth. Loss of APN expression by the host and/ or the malignant cells also impaired lung metastasis in experimental mouse models. Thus, cooperation in APN expression by both cancer cells and nonmalignant stromal cells within the tumor microenvironment promotes angiogenesis, tumor growth, and metastasis.
AB - Processes that promote cancer progression such as angiogenesis require a functional interplay between malignant and nonmalignant cells in the tumor microenvironment. The metalloprotease aminopeptidase N (APN; CD13) is often overexpressed in tumor cells and has been implicated in angiogenesis and cancer progression. Our previous studies of APN-null mice revealed impaired neoangiogenesis in model systems without cancer cells and suggested the hypothesis that APN expressed by nonmalignant cells might promote tumor growth. We tested this hypothesis by comparing the effects of APN deficiency in allografted malignant (tumor) and nonmalignant (host) cells on tumor growth and metastasis in APNnull mice. In two independent tumor graft models, APN activity in both the tumors and the host cells cooperate to promote tumor vascularization and growth. Loss of APN expression by the host and/ or the malignant cells also impaired lung metastasis in experimental mouse models. Thus, cooperation in APN expression by both cancer cells and nonmalignant stromal cells within the tumor microenvironment promotes angiogenesis, tumor growth, and metastasis.
KW - Lung cancer
KW - Melanoma
KW - Proteolytic activity
KW - ShRNA
KW - Tumorigenesis
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UR - http://www.scopus.com/inward/citedby.url?scp=84863171290&partnerID=8YFLogxK
U2 - 10.1073/pnas.1120790109
DO - 10.1073/pnas.1120790109
M3 - Article
C2 - 22307623
AN - SCOPUS:84863171290
SN - 0027-8424
VL - 109
SP - 1637
EP - 1642
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 5
ER -