Highlights of This Issue

DOI: Published November 2011

SDF-1α, PDGF-B, and BM-Derived Pericyte Differentiation

Hamdan et al. Page 1462

Pericytes are critical in remodeling and stabilizing developing tumor vessels. PDGF-B induces pericyte migration and differentiation and is upregulated in several tumor types. Hamdan and colleagues show that increased PDGF-B in the tumor microenvironment is mediated by the production of SDF-1α. SDF-1α upregulated PDGF-B mRNA and protein in vitro and in vivo, whereas a specific shRNA downregulated PDGF-B. Luciferase and ChIP assays showed that PDGF-B induction by SDF-1α was transcriptionally mediated, involving binding of ELK-1 to the pdgf-b promoter. This SDF-1α/PDGF-B pathway induced bone marrow cells to differentiate into pericytes and may therefore become a new therapeutic target to inhibit vasculogenesis.

Regulation of Semaphorin 3 in Cancer

Nguyen et al. Page 1479

Class 3 semaphorins have been shown to have tumor suppressive activities. In the current study, Nguyen and colleagues explored the role and regulation of SEMA3B and SEMA3F in endometrial cancer. Data showed a progressive decrease in SEMA3B and SEMA3F expression in human endometrial cancers. Treatment of endometrial cancer cell lines with progesterone or vitamin D restored the expression of SEMA3B and SEMA3F in cancer cells and inhibited growth and angiogenesis, suggesting that malignant behavior of cells can be reverted to their normal state by restoration of SEMA3 expression.

miR-31 Regulates Several Integrins

Augoff et al. Page 1500

MicroRNAs regulate gene expression by repression or degradation of mRNA of multiple target genes and, therefore, play an important role in angiogenesis, cell migration and invasion, especially in cancer. Changes in cell morphology and mobility are tightly regulated by the heterodimeric adhesion receptors, the integrins, whose bidirectional signaling function is crucial for both physiological and pathological conditions. Here, Augoff and coworkers show that miR-31, a key regulator of the cancer invasion-metastasis cascade, targets several α and β integrin subunits to suppress cell spreading in a ligand-specific manner in cancer cells.

IL-1-Regulated Growth and Inflammation in Melanoma

Qin et al. Page 1537

Melanoma secretes high levels of proinflammatory cytokines, including IL-1. To date, the expression of IL-1α and IL-1β in human melanoma and their functions and role(s) associated with tumor progression have yet to be elucidated. Here, Qin and colleagues examined IL-1α and IL-1β expression profiles in large-scale melanoma tissue samples and identified several important downstream molecules and kinase responders (SPAK/JNK) for endogenous IL-1 in human melanoma cells. This study suggests that IL-1α and IL-1β increase significantly from nevus to primary melanoma and interrupting IL-1 signaling can affect autophagy and inhibit growth of IL-1-positive melanoma cells.