Osteoblast-secreted collagen upregulates paracrine Sonic hedgehog signaling by prostate cancer cells and enhances osteoblast differentiation.

Molecular Cancer
Samantha M ZunichMarilyn L G Lamm

Abstract

Induction of osteoblast differentiation by paracrine Sonic hedgehog (Shh) signaling may be a mechanism through which Shh-expressing prostate cancer cells initiate changes in the bone microenvironment and promote metastases. A hallmark of osteoblast differentiation is the formation of matrix whose predominant protein is type 1 collagen. We investigated the formation of a collagen matrix by osteoblasts cultured with prostate cancer cells, and its effects on interactions between prostate cancer cells and osteoblasts. In the presence of exogenous ascorbic acid (AA), a co-factor in collagen synthesis, mouse MC3T3 pre-osteoblasts in mixed cultures with human LNCaP prostate cancer cells or LNCaP cells modified to overexpress Shh (LNShh cells) formed collagen matrix with distinct fibril ultrastructural characteristics. AA increased the activity of alkaline phosphatase and the expression of the alkaline phosphatase gene Akp2, markers of osteoblast differentiation, in MC3T3 pre-osteoblasts cultured with LNCaP or LNShh cells. However, the AA-stimulated increase in Akp2 expression in MC3T3 pre-osteoblasts cultured with LNShh cells far exceeded the levels observed in MC3T3 cells cultured with either LNCaP cells with AA or LNShh cells withou...Continue Reading

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Citations

Nov 2, 2013·Cytotherapy·Siti Norhaiza HadzirShahrul Hisham Zainal Ariffin
Sep 12, 2015·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Patrick AghajanianSubburaman Mohan
Aug 26, 2014·Bone Marrow Research·Fakher RahimNajmaldin Saki
Dec 18, 2012·Oncoimmunology·Michelle A Hurchla, Katherine N Weilbaecher
Sep 16, 2017·Pediatric Research·Philip M IannacconeArun K Sharma
Sep 5, 2018·Asian Journal of Andrology·Chun-Jung LinJer-Tsong Hsieh
May 24, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Shian-Ren LinYen-Nien Liu
Apr 28, 2015·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Sunil Kumar BodaBikramjit Basu

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Methods Mentioned

BETA
transmission electron microscopy
light microscopy
fluorescence microscopy
PCR
Assay

Software Mentioned

Adobe Photoshop
Primer Express
Improvision Openlab

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