PRL-3 Initiates Tumor Angiogenesis by Recruiting Endothelial Cells In vitro and In vivo

Abstract

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. (Cancer Res 2006; 66(19): 9625-35)

A role of autophagy in PTP4A3-driven cancer progression

“…32 In cells with stable ATG5 knockdown, PTP4A3 was unable to promote LC3 conversion upon CQ, rapamycin, or combined CQ and rapamycin treatments (Fig. 3C, red boxes in lanes 2, 8, 14 vs. blue boxes in lanes 5,11,17). Taken together, our results show that PTP4A3 promotes autophagic flux in an ATG5-dependent manner.…”

“…[13][14][15] PTP4A3 also promotes cell proliferation, angiogenesis, and cell-cycle progression. [16][17][18] More importantly, PTP4A3 is upregulated in clinically malignant cancer specimens compared with their benign counterparts in multiple human cancers and is associated with poor prognosis. 12,16,19,20 Recently, endosomes were shown to play an important function in autophagy, fusing with autophagosomes prior to lysosomal fusion for cargo degradation.…”

Snail as a key regulator of PRL-3 gene in colorectal cancer

“…[1][2][3][4][5][6] However, no mutation of human PRL-3 gene in CRC and other types of cancer has been reported. The mechanisms leading to elevated expression of PRL-3 in CRC and other kinds of cancer remain largely unknown.…”

Phosphatase of regenerating liver‐3 as a convergent therapeutic target for lymph node metastasis in esophageal squamous cell carcinoma

“…9,10 PRL-3 can promote cancer invasion, migration, growth, and angiogenesis, through either dephosphorylation that is catalyzed by catalytic domain or localization to plasma membrane directed by COOH-terminal prenylation motif. [11][12][13] Thus, PRL-3 plays crucial roles in the multiple steps of metastasis. In ESCC, the correlation between PRL-3 mRNA overexpression and LNM has recently been reported.…”