Browsing by Author "Liu, Ju-Fang"

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Osteoblast-secreted WISP-1 promotes adherence of prostate cancer cells to bone via the VCAM-1/integrin alpha 4 beta 1 system
(2018-01-01)
Chang, An-Chen
;
Chen, Po-Chun
;
Lin, Yu-Feng
;
Su, Chen-Ming
;
Liu, Ju-Fang
Bone metastasis is a frequent occurrence in prostate cancer (PCa) that is associated with severe complications such as fracture, bone pain and hypercalcemia. The cross-talk between metastatic cancer cells and bone is critical to the development and progression of bone metastases. In our previous data, we have described how the involvement of the Wnt-induced secreted protein-1/vascular cell adhesion molecule-1 (WISP-1/VCAM-1) system in this tumor bone interaction contributes to human PCa cell motility. In this study, we found that WISP-1 regulates bone mineralization by inducing bone morphogenetic protein-2 (BMP2), BMP4 and osteopontin (OPN) expression in osteoblasts. We also found that WISP-1 inhibited RANKL-dependent osteoclastogenesis. Moreover, osteoblast-derived WISP-1 enhanced VCAM-1 expression in PCa cells and subsequently promoted the adherence of cancer cells to osteoblasts. Furthermore, endothelin-1 (ET-1) expression in PCa cells was regulated by osteoblast-derived WISP-1, which promoted integrin alpha 4 beta 1 expression in osteoblasts via the MAPK pathway. Pretreatment of PCa cells with VCAM-1 antibody or osteoblasts with integrin alpha 4 beta 1 antibody attenuated the adherence of PCa cells to osteoblasts, suggesting that integrin alpha 4 beta 1 serves as a ligand that captures VCAM-1(+) metastatic tumor cells adhering to osteoblasts. Our findings reveal that osteoblast-derived WISP-1 plays a key role in regulating the adhesion of PCa cells to osteoblasts via the VCAM-1/integrin alpha 4 beta 1 system. Osteoblast-derived WISP-1 is a promising target for the prevention and inhibition of PCa-bone interaction. (C) 2018 Elsevier B.V. All rights reserved.
Thrombospondin 2 promotes tumor metastasis by inducing matrix metalloproteinase-13 production in lung cancer cells
(2018-09-01)
Liu, Ju-Fang
;
Lee, Chiang-Wen
;
Tsai, Ming-Horng
;
Tang, Chih-Hsin
;
Chen, Po-Chun
Thrombospondin (TSP)-2, a matricellular glycoprotein of the TSP family, regulates multiple biological functions, including proliferation, angiogenesis, cell adhesion, and extracellular matrix (ECM) modeling. The clinical relevance of TSP-2 has been explored in many different cancers. TSP-2 expression levels vary between different cancer types, and their role in tumor progression remains controversial. Although previous studies have reported higher serum TSP-2 levels in patients with non-small cell lung cancer, the role of TSP-2 in lung cancer progression remains to be addressed. A total of 585 lung adenocarcinoma datasets, including mRNA sequencing and clinical data, were retrieved from The Cancer Genome Atlas (TCGA). Forty paired adjacent normal tissues and lung tumor tissue datasets were used to examine TSP-2 expression levels. Tumor microarray were performed with immunohistochemical staining to examine TSP-2 expression in lung cancer patients. Transwell migration assay, quantitative real-time PCR and Western blot were used to investigate molecular mechanism of TSP-2 in lung cancer cell. TSP-2 promotes matrix metalloproteinase-13 (MMP-13) expression, cell migration, and cell invasion by mediating integrin alpha v beta 3/FAK/Akt/NF-kappa B signal transduction. Using TSP-2 knockdown stable cell lines, we found that TSP-2 knockdown reduces MMP-13 expression and cell mobility. When we manipulated the tumor tissue microarray and TCGA datasets to investigate the clinical relevance of TSP-2, we found high TSP-2 expression levels in lung cancer specimens. The present study demonstrates that TSP-2 regulates cell mobility through MMP-13 expression in lung cancer cells. In addition, TSP-2 expression was associated with MMP-13 expression and poor prognosis in lung cancer. TSP-2 may therefore be a promising novel target for lung cancer treatment.