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The role of sphingosine kinase 2 in promoting multiple myeloma cell invasive growth
Author(s) -
Zhang Hannah,
Zhao Derrick,
Li Xiaojiaoyang,
Liu Runping,
Wang Xuan,
Zhou Huiping
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.804.44
Subject(s) - sphingosine kinase 1 , sphingosine , sphingosine kinase , cell growth , cancer research , annexin , sphingosine 1 phosphate , apoptosis , kinase , microbiology and biotechnology , biology , flow cytometry , chemistry , biochemistry , receptor
Multiple myeloma (MM) is a heterogeneous disease with a prognosis that varies with patient genetics, disease burden, tumor biology, and treatments. Effective therapy for high risk MM is currently unavailable due to the limited understanding of its pathophysiology. Sphingosine 1‐phosphate (S1P) has been identified as an important signaling molecule involved in regulating various cancer cell growths. Two protein kinases responsible for S1P synthesis, sphingosine kinase 1 and 2 (SphK1 and SphK2), have been identified. During the last decade, numerous studies have shown that SphK1 plays a critical role in promoting various cancer cell growths. However, only limited attention has been paid to SphK2. Our recent studies reported that activation of SphK2 is linked to invasive growth of cholangiocarcinoma. However, the role of SphK2 in MM cell growth is not clear and is the focus of this study. Methods Studies were conducted in the human MM cell lines, KMS‐11, KMS‐12BM, KMS‐20, KMS‐21BM, KMS‐26, KMS‐28BM, KMS‐34, MOLP‐8, LP‐1, MM.1S. The expression of SphK1 and SphK2 was determined by real‐time RT‐PCR and Western blot analysis and confirmed by DNA sequencing. The SphK2 inhibitor, K145, and gene‐specific shRNA were used to inhibit SphK2 activation and expression. Cell proliferation was determined using a CCK‐8 kit. Cell apoptosis was analyzed by Annexin V‐FITC/PI staining followed by flow cytometry. Results The expression level of SphK2 in all tested MM cell lines was significantly higher than SphK1. S1P significantly induced proliferation and growth of MM cells, which was inhibited by K145 as well as gene specific shRNA targeting SphK2. The SphK2 expression level is correlated to invasiveness of MM cell growth and its sensitivity to K145. Discussion/Conclusion SphK1 and SphK2 are all expressed in human MM cancer cells. However, the SphK2 expression level is much higher than SphK1. In this study, we were able to show that SphK2 plays a critical role in S1P‐mediated invasive growth of MM cells. The results in this study suggest that targeting SphK2 may represent a novel therapy for MM. Support or Funding Information This work was partially supported by National Institutes of Health Grant R01 DK104893 and R01DK‐057543; VA Merit Award I01BX001390; National Natural Science Foundation of China Grants 81070245 and 81270489. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .