Association of insulin-like growth factor binding protein-3 expression with melanoma progression

Abstract

Previous studies from our laboratory have identified several endothelial cell -associated marker genes implicated in human melanoma metastasis via tumor vasculogenic mimicry. In this study, we used dual model systems composed of melanoma cell lines and clinical melanoma samples to validate the importance of insulin-like growth factor binding protein-3 (IGFBP-3) as a marker involved in disease progression. Gene expression analysis was done using a microarray approach for both primary and metastatic melanoma samples. The expression of IGFBP-3 was decreased using a small interfering RNA (siRNA) knockdown approach and quantified with real-time quantitative reverse transcription-PCR analysis. The expression of insulin-like growth factor binding protein 3 (IGFBP-3) was up-regulated by nearly 16-fold in WM266-4 compared with WM35 cells. A subsequent parallel analysis using freshly isolated primary and metastatic melanoma cell samples and melanoma tissue array confirmed the previous findings. The functional significance of IGFBP-3 in melanoma invasion was further investigated using a siRNA gene knockdown approach, with the expression of IGFBP-3 markedly reduced. Additionally, siRNA knockdown resulted in a significant reduction in cell motility, migration, and invasive capacity of WM266-4 cells in vitro. These results strongly suggest that IGFBP-3 expression may be a vital cell motility, migration, and proliferation factor necessary for melanoma metastasis and is an important biomarker in human melanoma. [Mol Cancer Ther 2006;5(12):3078 -84]

STAT-1 expression is regulated by IGFBP-3 in malignant glioma cells and is a strong predictor of poor survival in patients with glioblastoma

“…Similar to our findings, which showed that IGFBP-3 is involved in malignant glioma cell motility and migration, an earlier report has shown that IGFBP-3 is essential for the migration of melanoma cells. 59 On the contrary, some studies have shown IGFBP-3 significantly reduces the migration of PC3 prostate cancer cells, Ewing's sarcoma cells, and non-small cell lung cancers, further emphasizing the multifunctional roles of IGFBP-3 in different human cancers. 4,35,38 Our results demonstrating IGFBP-3's involvement in GBM tumor cell invasion in vitro are also consistent with the findings of previous studies on malignant melanoma and esophageal squamous cell carcinoma.…”

miRNAs in the Biology of Cancers and Viral Infections

“…Indeed, besides miR-15a and miR-16-1, other miRNAs such as miR-183, miR-190, miR-24-1 and miR-213 are known to have reduced expression in B-CLL [25]. Other than B-CLL, changes in miRNA expression have also been documented for other cancers [22,26]; hence, miR-143 and miR-145 are significantly reduced in colorectal cancers [27]. Taken together, extant findings are consistent with a general role played by various miRNAs in many neoplasms.…”

Involvement of Insulin-like Growth Factor-binding Protein-3 in the Effects of Histone Deacetylase Inhibitor MS-275 in Hepatoma Cells

“…There are reports of IGFBP-3 overexpression in squamous cell lung cancer (26), localized prostate cancer (27), pancreatic adenocarcinoma (28), clear cell renal cell carcinoma (29), metastatic melanoma (30), and breast cancers with poor prognosis (31). In contrast, in patients with HCC, IGFBP-3 mRNA is consistently expressed at a lower level in tumor tissue than in healthy liver (3,16).…”

“…Whereas inhibitory effects have been observed in endometrioid ovarian cancer (42), Ewing's sarcoma (43), and non-small cell lung cancer cells (44), IGFBP-3 can induce migration in melanoma (30) and breast cancer (38) cells, as well as umbilical vein (45) and retinal (46) endothelial cells. Furthermore, increased IGFBP-3 expression has been observed in liver and lymph node metastases of pancreatic endocrine neoplasms (47), although it is antimetastatic in lung cancer (44).…”