PRL-3 initiates tumor angiogenesis by recruiting endothelial cells in vitro and in vivo.
We show here that PRL-3 protein is expressed in fetal heart, developing blood vessels, and pre-erythrocytes but not in their mature counterparts. These observations imply that PRL-3 may be involved in the early development of the circulatory system. Because PRL-3 mRNA had been reported to be consistently elevated in metastatic samples derived from colorectal cancers, we attempted to investigate if PRL-3 might be involved in tumor angiogenesis and if PRL-3-expressing cells could cross-talk to human umbilical vascular endothelial cells (HUVEC) by using an in vitro coculture system. HUVECs were grown with fibroblasts, which were later overlaid with PRL-3-expressing cells. We observed that both PRL-3-expressing Chinese hamster ovary (CHO) cells and PRL-3-expressing DLD-1 human colon cancer cells could redirect the migration of HUVECs toward them; in addition, PRL-3-expressing DLD-1 cells could enhance HUVEC vascular formation. In vivo injection of PRL-3-expressing CHO cells into nude mice to form local tumors resulted in the recruitment of host endothelial cells into the tumors and initiation of angiogenesis. We further showed that PRL-3-expressing cells reduced interleukin-4 (IL-4) expression levels and thus attenuated IL-4 inhibitory effects on the HUVEC vasculature. Our findings provide direct evidence that PRL-3 may be involved in triggering angiogenesis and establishing microvasculature and it may serve as an attractive therapeutic target with respect to both angiogenesis and cancer metastasis.
Guo
Ke
K
Institute of Molecular and Cell Biology, Singapore, Singapore.
Li
Jie
J
Wang
Haihe
H
Osato
Motomi
M
Tang
Jing Ping
JP
Quah
Samantha Yiling
SY
Gan
Bin Qi
BQ
Zeng
Qi
Q
D000818:Animals; D001808:Blood Vessels / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D016466:CHO Cells / Q000378:metabolism / Q000637:transplantation; D002465:Cell Movement / Q000502:physiology; D018920:Coculture Techniques; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000473:pathology; D006224:Cricetinae; D003412:Cricetulus; D042783:Endothelial Cells / Q000166:cytology*; D005318:Fetal Heart / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008175:Lung Neoplasms / Q000556:secondary; D051379:Mice; D009206:Myocardium / Q000378:metabolism; D009363:Neoplasm Proteins / Q000502:physiology*; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000502:physiology; D013498:Suramin / Q000494:pharmacology
D017874:Immediate-Early Proteins; D009363:Neoplasm Proteins; C111534:Ptp4a3 protein, mouse; D011993:Recombinant Fusion Proteins; D015847:Interleukin-4; D013498:Suramin; C524057:PRL-3 protein, rat; C484730:PTP4A3 protein, human; D017027:Protein Tyrosine Phosphatases