PRL-3 initiates tumor angiogenesis by recruiting endothelial cells in vitro and in vivo

• Published in: Cancer research (Chicago, Ill.) Vol. 66; no. 19; pp. 9625 - 9635
• Main Authors: KE GUO, JIE LI, HAIHE WANG, OSATO, Motomi, JING PING TANG, QUAH, Samantha Yiling, BIN QI GAN, QI ZENG
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.10.2006
• Subjects: Animals; Antineoplastic agents; Biological and medical sciences; Blood Vessels - embryology; Blood Vessels - growth & development; Blood Vessels - metabolism; Cell Movement - physiology; CHO Cells - metabolism; CHO Cells - transplantation; Coculture Techniques; Colorectal Neoplasms - blood supply; Colorectal Neoplasms - pathology; Cricetinae; Cricetulus; Endothelial Cells - cytology; Fetal Heart - metabolism; Gene Expression Regulation, Developmental; Hematopoiesis - genetics; Hematopoiesis - physiology; Hematopoietic Stem Cells - metabolism; Humans; Immediate-Early Proteins - biosynthesis; Immediate-Early Proteins - genetics; Interleukin-4 - antagonists & inhibitors; Interleukin-4 - biosynthesis; Lung Neoplasms - secondary; Medical sciences; Mice; Myocardium - metabolism; Neoplasm Proteins - physiology; Neovascularization, Pathologic - drug therapy; Neovascularization, Pathologic - metabolism; Neovascularization, Pathologic - physiopathology; Neovascularization, Physiologic - genetics; Neovascularization, Physiologic - physiology; Pharmacology. Drug treatments; Protein Tyrosine Phosphatases - biosynthesis; Protein Tyrosine Phosphatases - genetics; Protein Tyrosine Phosphatases - physiology; Rats; Recombinant Fusion Proteins - physiology; Suramin - pharmacology; Tumors; Angiogenesis; In vivo; Endothelial cell; Neovascularization; Malignant tumor; In vitro
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.can-06-0726

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.