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TOPK is highly expressed in circulating tumor cells, enabling metastasis of prostate cancer.

Sun H, Zhang L, Shi C, Hu P, Yan W, Wang Z, Duan Q, Lu F, Qin L, Lu T, Xiao J, Wang Y, Zhu F, Shao C - Oncotarget (2015)

Bottom Line: Herein, we established a xenograft animal model, isolated and cultured the CTCs, and found CTCs have significantly greater migratory capacity than parental cells.TOPK is more highly expressed in the CTCs than in parental cells and is also highly expressed in the metastatic nodules caused by CTCs in mice.Knocking down TOPK decreased the migration of CTCs both in vitro and in vivo.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Xijing Hospital, The Fourth Military Medical University, Xian, China.

ABSTRACT
Circulating tumor cells (CTCs) are important for metastasis in prostate cancer. T-LAK cell-originated protein kinase (TOPK) is highly expressed in cancer cells. Herein, we established a xenograft animal model, isolated and cultured the CTCs, and found CTCs have significantly greater migratory capacity than parental cells. TOPK is more highly expressed in the CTCs than in parental cells and is also highly expressed in the metastatic nodules caused by CTCs in mice. Knocking down TOPK decreased the migration of CTCs both in vitro and in vivo. TOPK was modulated by the PI3K/PTEN and ERK pathways during the metastasis of prostate cancer. High levels of TOPK in the tumors of patients were correlated with advanced stages of prostate cancer, especially for high-risk patients of Gleason score≥8, PSA>20ng/ml. In summary, TOPK was speculated to be one of a potential marker and therapeutic target in advanced prostate cancer.

No MeSH data available.


Related in: MedlinePlus

Knocking down TOPK in CTCs decreased their metastatic capacityA. Expression of TOPK in the CTCshTOPK and CTCshMOCK cell lines. B. Scratch assays performed in CTCshTOPK and CTCshMOCK cells showed that CTCshMOCK cells migrate faster than CTCshTOPK cells. C. Transwell assays of CTCshTOPK (right) and CTCshMOCK (left) cells showed that CTCshMOCK cells have greater invasive capacity than CTCshTOPK cells. D. The metastatic capacity of CTCshTOPK and CTCshMOCK cells in vivo. (D1) Gross examination revealed increased numbers of visible metastatic tumor nodules in the lungs of mice from the CTCshMOCK group compared to the lungs of mice from the CTCshTOPK group. Lungs of mice from the CTCshMOCK group also showed focal hemorrhages (dark red areas of lung surfaces). Arrows indicate tumor metastatic nodules. (D2) Hematoxylin/eosin-stained lung sections from mice injected intravenously with either CTCshMOCK or CTCshTOPK cells. In the CTCshMOCK group, metastatic tumors presented as multifocal nodules, whereas only focal microscopically visible metastases were found in the CTCshTOPK group. Magnification, 40× and 400×. (D3) Immunohistochemical analysis of TOPK expression in pulmonary metastatic nodules. CTCshTOPK metastatic tumor cells showed strong nuclear and cytoplasmic expression of TOPK, whereas normal pulmonary alveolar epithelial cells showed no or very weak expression of TOPK. Magnification, 40× and 400×. E. The expression of phospho-PTEN, phospho-AKT, and phospho-ERK in CTCshTOPK and CTCshMOCK cells.
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Figure 4: Knocking down TOPK in CTCs decreased their metastatic capacityA. Expression of TOPK in the CTCshTOPK and CTCshMOCK cell lines. B. Scratch assays performed in CTCshTOPK and CTCshMOCK cells showed that CTCshMOCK cells migrate faster than CTCshTOPK cells. C. Transwell assays of CTCshTOPK (right) and CTCshMOCK (left) cells showed that CTCshMOCK cells have greater invasive capacity than CTCshTOPK cells. D. The metastatic capacity of CTCshTOPK and CTCshMOCK cells in vivo. (D1) Gross examination revealed increased numbers of visible metastatic tumor nodules in the lungs of mice from the CTCshMOCK group compared to the lungs of mice from the CTCshTOPK group. Lungs of mice from the CTCshMOCK group also showed focal hemorrhages (dark red areas of lung surfaces). Arrows indicate tumor metastatic nodules. (D2) Hematoxylin/eosin-stained lung sections from mice injected intravenously with either CTCshMOCK or CTCshTOPK cells. In the CTCshMOCK group, metastatic tumors presented as multifocal nodules, whereas only focal microscopically visible metastases were found in the CTCshTOPK group. Magnification, 40× and 400×. (D3) Immunohistochemical analysis of TOPK expression in pulmonary metastatic nodules. CTCshTOPK metastatic tumor cells showed strong nuclear and cytoplasmic expression of TOPK, whereas normal pulmonary alveolar epithelial cells showed no or very weak expression of TOPK. Magnification, 40× and 400×. E. The expression of phospho-PTEN, phospho-AKT, and phospho-ERK in CTCshTOPK and CTCshMOCK cells.

Mentions: In order to further confirm the role of TOPK prostate cancer metastasis, TOPK was knocked down in CTCs through lentiviral transfection. Western blotting demonstrated that the expression of TOPK in CTCshTOPK cells decreased much more remarkably than that in CTCshMOCK cells (Figure 4A).


TOPK is highly expressed in circulating tumor cells, enabling metastasis of prostate cancer.

Sun H, Zhang L, Shi C, Hu P, Yan W, Wang Z, Duan Q, Lu F, Qin L, Lu T, Xiao J, Wang Y, Zhu F, Shao C - Oncotarget (2015)

Knocking down TOPK in CTCs decreased their metastatic capacityA. Expression of TOPK in the CTCshTOPK and CTCshMOCK cell lines. B. Scratch assays performed in CTCshTOPK and CTCshMOCK cells showed that CTCshMOCK cells migrate faster than CTCshTOPK cells. C. Transwell assays of CTCshTOPK (right) and CTCshMOCK (left) cells showed that CTCshMOCK cells have greater invasive capacity than CTCshTOPK cells. D. The metastatic capacity of CTCshTOPK and CTCshMOCK cells in vivo. (D1) Gross examination revealed increased numbers of visible metastatic tumor nodules in the lungs of mice from the CTCshMOCK group compared to the lungs of mice from the CTCshTOPK group. Lungs of mice from the CTCshMOCK group also showed focal hemorrhages (dark red areas of lung surfaces). Arrows indicate tumor metastatic nodules. (D2) Hematoxylin/eosin-stained lung sections from mice injected intravenously with either CTCshMOCK or CTCshTOPK cells. In the CTCshMOCK group, metastatic tumors presented as multifocal nodules, whereas only focal microscopically visible metastases were found in the CTCshTOPK group. Magnification, 40× and 400×. (D3) Immunohistochemical analysis of TOPK expression in pulmonary metastatic nodules. CTCshTOPK metastatic tumor cells showed strong nuclear and cytoplasmic expression of TOPK, whereas normal pulmonary alveolar epithelial cells showed no or very weak expression of TOPK. Magnification, 40× and 400×. E. The expression of phospho-PTEN, phospho-AKT, and phospho-ERK in CTCshTOPK and CTCshMOCK cells.
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Related In: Results  -  Collection

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Figure 4: Knocking down TOPK in CTCs decreased their metastatic capacityA. Expression of TOPK in the CTCshTOPK and CTCshMOCK cell lines. B. Scratch assays performed in CTCshTOPK and CTCshMOCK cells showed that CTCshMOCK cells migrate faster than CTCshTOPK cells. C. Transwell assays of CTCshTOPK (right) and CTCshMOCK (left) cells showed that CTCshMOCK cells have greater invasive capacity than CTCshTOPK cells. D. The metastatic capacity of CTCshTOPK and CTCshMOCK cells in vivo. (D1) Gross examination revealed increased numbers of visible metastatic tumor nodules in the lungs of mice from the CTCshMOCK group compared to the lungs of mice from the CTCshTOPK group. Lungs of mice from the CTCshMOCK group also showed focal hemorrhages (dark red areas of lung surfaces). Arrows indicate tumor metastatic nodules. (D2) Hematoxylin/eosin-stained lung sections from mice injected intravenously with either CTCshMOCK or CTCshTOPK cells. In the CTCshMOCK group, metastatic tumors presented as multifocal nodules, whereas only focal microscopically visible metastases were found in the CTCshTOPK group. Magnification, 40× and 400×. (D3) Immunohistochemical analysis of TOPK expression in pulmonary metastatic nodules. CTCshTOPK metastatic tumor cells showed strong nuclear and cytoplasmic expression of TOPK, whereas normal pulmonary alveolar epithelial cells showed no or very weak expression of TOPK. Magnification, 40× and 400×. E. The expression of phospho-PTEN, phospho-AKT, and phospho-ERK in CTCshTOPK and CTCshMOCK cells.
Mentions: In order to further confirm the role of TOPK prostate cancer metastasis, TOPK was knocked down in CTCs through lentiviral transfection. Western blotting demonstrated that the expression of TOPK in CTCshTOPK cells decreased much more remarkably than that in CTCshMOCK cells (Figure 4A).

Bottom Line: Herein, we established a xenograft animal model, isolated and cultured the CTCs, and found CTCs have significantly greater migratory capacity than parental cells.TOPK is more highly expressed in the CTCs than in parental cells and is also highly expressed in the metastatic nodules caused by CTCs in mice.Knocking down TOPK decreased the migration of CTCs both in vitro and in vivo.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Xijing Hospital, The Fourth Military Medical University, Xian, China.

ABSTRACT
Circulating tumor cells (CTCs) are important for metastasis in prostate cancer. T-LAK cell-originated protein kinase (TOPK) is highly expressed in cancer cells. Herein, we established a xenograft animal model, isolated and cultured the CTCs, and found CTCs have significantly greater migratory capacity than parental cells. TOPK is more highly expressed in the CTCs than in parental cells and is also highly expressed in the metastatic nodules caused by CTCs in mice. Knocking down TOPK decreased the migration of CTCs both in vitro and in vivo. TOPK was modulated by the PI3K/PTEN and ERK pathways during the metastasis of prostate cancer. High levels of TOPK in the tumors of patients were correlated with advanced stages of prostate cancer, especially for high-risk patients of Gleason score≥8, PSA>20ng/ml. In summary, TOPK was speculated to be one of a potential marker and therapeutic target in advanced prostate cancer.

No MeSH data available.


Related in: MedlinePlus