Cooperative effects of aminopeptidase N (CD13) expressed by nonmalignant and cancer cells within the tumor microenvironment.
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 APN-null 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.
David H Koch Center, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Liliana
L
Guzman-Rojas
Roberto
R
Rangel
Ahmad
A
Salameh
Julianna K
JK
Edwards
Eleonora
E
Dondossola
Yun-Gon
YG
Kim
Alan
A
Saghatelian
Ricardo J
RJ
Giordano
Mikhail G
MG
Kolonin
Fernanda I
FI
Staquicini
Erkki
E
Koivunen
Richard L
RL
Sidman
Wadih
W
Arap
Renata
R
Pasqualini
D000818:Animals; D018826:CD13 Antigens / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
D018826:CD13 Antigens