Acidic extracellular pH promotes prostate cancer bone metastasis by enhancing PC-3 stem cell characteristics, cell invasiveness and VEGF-induced vasculogenesis of BM-EPCs

  • Authors:
    • Sheng Huang
    • Yubo Tang
    • Xinsheng Peng
    • Xingdong Cai
    • Qingde Wa
    • Dong Ren
    • Qiji Li
    • Jiaquan Luo
    • Liangping Li
    • Xuenong Zou
    • Shuai Huang
  • View Affiliations

  • Published online on: August 2, 2016     https://doi.org/10.3892/or.2016.4997
  • Pages: 2025-2032
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Abstract

Bone metastasis is a main cause of cancer-related mortality in patients with advanced prostate cancer. Emerging evidence suggests that the acidic extracellular microenvironment plays significant roles in the growth and metastasis of tumors. However, the effects of acidity on bone metastasis of PCa remain undefined. In the present study, PC-3 cells were cultured in acidic medium (AM; pH 6.5) or neutral medium (NM; pH 7.4), aiming to investigate the effects and possible mechanisms of acidic extracellular microenvironment in bone metastasis of PCa. Our results showed that AM can promote spheroid and colony formations, cell viability and expression of stem cell characteristic-related markers in PC-3 cells. Moreover, AM stimulates MMP-9 secretion and promotes invasiveness of PC-3 cells, and these effects can be inhibited by blocking of MMP-9. Furthermore, AM stimulates VEGF secretion of PC-3 and AM conditioned medium (CMAM) promotes vasculogenesis of BM-EPCs by increasing cell viability, migration, tube formation, which involved activating the phosphorylation of VEGFR-2, Akt and P38, when pH of NM conditioned medium (CMNM) was modulated the same as AM conditioned medium (CMAM). Further studies have shown that CMNM induced vasculogenesis of BM-EPCs can be inhibited by the inhibition of VEGFR2 with DMH4. These findings suggest that acidic extracellular microenvironment may have the potential to modulate prostate cancer bone metastasis by enhancing PC-3 stem cell characteristics, cell invasiveness and VEGF-induced vasculogenesis of BM-EPCs. Improved anticancer strategies should be designed to selectively target acidic tumor microenvironment.
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October-2016
Volume 36 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Huang S, Tang Y, Peng X, Cai X, Wa Q, Ren D, Li Q, Luo J, Li L, Zou X, Zou X, et al: Acidic extracellular pH promotes prostate cancer bone metastasis by enhancing PC-3 stem cell characteristics, cell invasiveness and VEGF-induced vasculogenesis of BM-EPCs. Oncol Rep 36: 2025-2032, 2016
APA
Huang, S., Tang, Y., Peng, X., Cai, X., Wa, Q., Ren, D. ... Huang, S. (2016). Acidic extracellular pH promotes prostate cancer bone metastasis by enhancing PC-3 stem cell characteristics, cell invasiveness and VEGF-induced vasculogenesis of BM-EPCs. Oncology Reports, 36, 2025-2032. https://doi.org/10.3892/or.2016.4997
MLA
Huang, S., Tang, Y., Peng, X., Cai, X., Wa, Q., Ren, D., Li, Q., Luo, J., Li, L., Zou, X., Huang, S."Acidic extracellular pH promotes prostate cancer bone metastasis by enhancing PC-3 stem cell characteristics, cell invasiveness and VEGF-induced vasculogenesis of BM-EPCs". Oncology Reports 36.4 (2016): 2025-2032.
Chicago
Huang, S., Tang, Y., Peng, X., Cai, X., Wa, Q., Ren, D., Li, Q., Luo, J., Li, L., Zou, X., Huang, S."Acidic extracellular pH promotes prostate cancer bone metastasis by enhancing PC-3 stem cell characteristics, cell invasiveness and VEGF-induced vasculogenesis of BM-EPCs". Oncology Reports 36, no. 4 (2016): 2025-2032. https://doi.org/10.3892/or.2016.4997