Tumor microenvironment promotes prostate cancer cell dissemination via the Akt/mTOR pathway

Shi，Junlin1; Wang，Lihui1; Zou，Chunlin1; Xia，Yudui1; Qin，Siyuan1,2; Keller，Evan3; Mizokami，Atsushi4; Zhang，Jian2,3; Lu，Yi2

2018

10.18632/oncotarget.24104

ONCOTARGET   影响因子和分区

1949-2553

1949-2553

Metastasis causes high mortality in various malignancies, including prostate cancer (PCa). Accumulating data has suggested that cancer cells spread from the primary tumor to distant sites at early stage, which is characterized by disseminated tumor cells (DTCs). However, lack of direct evidence of partial localized PCa cells occurring epithelial-to-mesenchymal transition (EMT) and disseminating to distant sites (e.g bone marrow). In this study, we used luciferase labeled PCa cells to establish an EMT mouse model and to detect whether DTCs spread into the bone marrow. We observed tumor cells existing in mouse bone marrow when tumor grew subcutaneously at palpable stage. Studies also showed that ex vivo tumor cells exhibited increased proliferative, migratory, invasive and angiogenesis abilities. When compared ex vivo tumor cells with parental cells, hallmarks of EMT including E-cadherin, Vimentin, Snail, and ZO-1 were altered significantly. Specifically, the ex vivo tumor cells showed more mesenchymal properties. Angiogenesis markers, including VEGFR2, VEGFR3, MCP-3, I-TAC, I309, uPAR and GROa, were also increased in the ex vivo tumor cells. Intriguingly, MCP-1 expression was dramatically increased in those cells. Mechanistic analyses indicated that AP1 mediates PCa EMT and the appearance of DTCs via the Akt/mTOR pathway. This study may provide potential therapeutic targets and diagnostic biomarkers of PCa progression and metastasis.

Disseminated tumor cells Epithelial-mesenchymal transition Metastasis Prostate cancer Tumor microenvironment

英语

通讯

MOLECULAR BIOLOGY & GENETICS

2-s2.0-85041379235

Scopus

1.,Key Laboratory of Longevity and Aging-Related Diseases (Guangxi Medical University),Ministry of Education,Nanning,China
2.Southern University of Science and Technology School of Medicine,Shenzhen,China
3.,Department of Pathology and Internal Medicine,University of Michigan,Ann Arbor,United States
4.,Department of Urology,Graduate School of Medical Sciences,Kanazawa University,Kanazawa,Japan

Shi，Junlin,Wang，Lihui,Zou，Chunlin,et al. Tumor microenvironment promotes prostate cancer cell dissemination via the Akt/mTOR pathway[J]. ONCOTARGET,2018,9(10):9206-9218.

Shi，Junlin.,Wang，Lihui.,Zou，Chunlin.,Xia，Yudui.,Qin，Siyuan.,...&Lu，Yi.(2018).Tumor microenvironment promotes prostate cancer cell dissemination via the Akt/mTOR pathway.ONCOTARGET,9(10),9206-9218.

Shi，Junlin,et al."Tumor microenvironment promotes prostate cancer cell dissemination via the Akt/mTOR pathway".ONCOTARGET 9.10(2018):9206-9218.