Expression of Cyr61, CTGF, and WISP-1 Correlates with Clinical Features of Lung Cancer

Abstract

BackgroundCCN family, comprising six members (Cyr61, CTGF, Nov, WISP-1, WISP-2, WISP-3), is involved in the stimulation of cell proliferation, migration, adhesion, angiogenesis, and tumorigenesis. Several studies have shown that expression of Cyr61, CTGF, and WISP-1 affects the tumorigenic potential of lung cancer cells in vitro. However, the correlation of expression of CCN family proteins and clinical features of lung cancer remains unknown.Methodology and Principal FindingsIn the present work, we quantified the mRNA levels of Cyr61, CTGF, and WISP-1 in samples from 60 primary lung cancers and their matched normal lung tissues by quantitative real-time PCR assay. Downregulation of the Cyr61 and CTGF genes and upregulation of the WISP-1 gene were found in primary lung cancers compared to the paired normal lung tissues. Immunohistochemistry analysis also disclosed a similar expression pattern of Cyr61, CTGF, and WISP-1 protein in paired lung cancer tissues. Statistical analysis revealed significant associations between expression of either Cyr61 or CTGF with tumor stage, tumor histology, metastasis, smoking, and family history at diagnosis. A significant correlation also existed between WISP-1 expression with tumor histology, and patient age. Moreover, expression levels of Cyr61 and CTGF correlated with survival of the lung-cancer patients.ConclusionsOur results suggest that Cyr61, CTGF, and WISP-1 might be implicated in the development and progression of primary lung cancers, and their levels might serve as valuable prognostic markers, as well as potential targets for therapeutic intervention.

Kallikrein-related Peptidase 12 Hydrolyzes Matricellular Proteins of the CCN Family and Modifies Interactions of CCN1 and CCN5 with Growth Factors

“…The first one corresponds to the decreased expression of CCN1 in the tumor site, and the second one refers to the suppression of the tumor inhibitory effects of the residual CCN1 activity through KLK-mediated proteolysis. In addition to CCN1, CCN2 (62) and CCN5 (present study) are down-regulated, whereas CCN4 (62) is up-regulated in NSCLC. These findings indicate that members of the CCN family may play important but contrasting roles in NSCLC progression.…”

“…In particular in nonsmall cell lung carcinoma (NSCLC), this idea is supported by our findings showing that: (a) KLK12 is coexpressed with several CCNs in the cancerous tissue of patients and (b) full-length CCN1 and KLK12-released CCN1 fragments have different effects on the migration of the A549 lung cancer cell line in vitro. Previous data have indicated that CCN1 may act as a tumor suppressor in NSCLC in vitro and in vivo (61,62). Collectively, these findings suggest that two mechanisms affecting CCN1 could act simultaneously to facilitate NSCLC development.…”

Activation of Notch1 signaling in stromal fibroblasts inhibits melanoma growth by upregulating WISP-1

“…Potential involvements of WISP-1 in several cancers have been reported (Soon et al, 2003;Chen et al, 2007;Davies et al, 2007), whereas its role in melanoma remains unexplored. We sought to investigate the biological function of WISP-1 in melanoma.…”

Wnt activation is implicated in glioblastoma radioresistance

“…For example, WISP1, an effector of activated Wnt signaling previously reported to regulate cell survival, [17][18][19] showed the highest level change (3.6-fold higher in U373-IR than in U373-C). Patient data at the US National Cancer Institute (Repository of Molecular Brain Neoplasia Data (REMBRANDT) 20,21 ) also indicated that upregulation of WISP1 is associated with poorer clinical outcome (Supplementary Figure S2), further substantiating our data.…”