Angiogenesis Induced by Signal Transducer and Activator of Transcription 5A (STAT5A) Is Dependent on Autocrine Activity of Proliferin

Abstract

Background: FGFs activate STAT5 transcription factor. Results: In mouse endothelial cells, active STAT5 promotes the production and release of proliferin, which stimulates endothelial cell migration, invasion and tube formation in vitro, and angiogenesis in vivo. Conclusion: Proliferin is a secreted pro-angiogenic factor downstream of FGFs and STAT5. Significance: Proliferin is an autocrine factor likely relevant in physiologic and pathologic angiogenesis.

STAT5 and Prolactin Participate in a Positive Autocrine Feedback Loop That Promotes Angiogenesis

“…We chose brain endothelial cells because of the importance of angiogenesis in glioma progression and because of our longstanding interest in this tumor type. Consistent with our previously reported observations in mouse ECs (22,26), conditioned medium from CA-STAT5A-transduced cells compared with conditioned media from cells treated with empty virus or DN-STAT5A-transduced cells stimulates hCMEC/D3 tube formation (Fig. 1A) and migration (Fig.…”

“…Ko et al (41) observed testicular angiogenesis in response to systemic PRL expression and full-length PRL increases in vascular density in the chicken chorioallantoic membrane assay (5-7). The proangiogenic role of PRL family members appears to be conserved across species, with PLF fulfilling this role in mice (22,42).…”

“…Autocrine Pro-angiogenic Factor-We have recently shown that FGF-induced activation of STAT5 in mouse microvascular ECs results in the secretion of the growth hormone/prolactin family member PLF, which stimulates EC migration, invasion, and tube formation (22,26). Because the PLF gene does not exist in humans (21, 28 -30), we explored whether active STAT5 promotes the secretion of a different autocrine, proangiogenic activity in human ECs.…”

“…We have shown previously that PLF plays a pivotal role in angiogenesis induced by FGF/STAT5 in mouse brain microvascular endothelial cells (22). Because the PLF gene does not exist in humans and PRL appears to carry out many PLF functions, we sought to explore whether PRL or its family members carry out roles similar to PLF in human cells.…”

A Positive Feedback Loop Between Prolactin and Stat5 Promotes Angiogenesis

“…[14]. CA-STAT5 increases PLF1 transcript levels and binds to the PFL1 promoter region as determined by chromatin immunoprecipitation (ChIP) assay, suggesting that STAT5 participates directly in the transcriptional regulation of PFL1 [22].…”