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

Shi, Jianwu; Wang, Lihui; Zou, Chunlin; Xia, Yudui; Qin, Siyuan; Keller, Evan T.; Mizokami, Atsushi; Zhang, Jian; Lü, Yi

doi:10.18632/oncotarget.24104

Cited by 14 publications

(11 citation statements)

References 43 publications

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“…Despite these recent advances, treatments only provide scanty survival benefits and most patients develop disease relapse ( 183 ). Investigating on the mechanisms that may drive prostate cancer progression, different data reported that it is surrounded by a complex TME ( 184 , 185 ). In particular, MDSCs are the most renowned immune cells subset that has been reported to infiltrate the prostate TME ( 186 – 188 ).…”

Section: Mdscs In Prostate Cancermentioning

confidence: 99%

The New Era of Cancer Immunotherapy: Targeting Myeloid-Derived Suppressor Cells to Overcome Immune Evasion

2020

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Suppression of antitumor immune responses is one of the main mechanisms by which tumor cells escape from destruction by the immune system. Myeloid-derived suppressor cells (MDSCs) represent the main immunosuppressive cells present in the tumor microenvironment (TME) that sustain cancer progression. MDSCs are a heterogeneous group of immature myeloid cells with a potent activity against T-cell. Studies in mice have demonstrated that MDSCs accumulate in several types of cancer where they promote invasion, angiogenesis, and metastasis formation and inhibit antitumor immunity. In addition, different clinical studies have shown that MDSCs levels in the peripheral blood of cancer patients correlates with tumor burden, stage and with poor prognosis in multiple malignancies. Thus, MDSCs are the major obstacle to many cancer immunotherapies and their targeting may be a beneficial strategy for improvement the efficiency of immunotherapeutic interventions. However, the great heterogeneity of these cells makes their identification in human cancer very challenging. Since both the phenotype and mechanisms of action of MDSCs appear to be tumor-dependent, it is important to accurately characterized the precise MDSC subsets that have clinical relevance in each tumor environment to more efficiently target them. In this review we summarize the phenotype and the suppressive mechanisms of MDSCs populations expanded within different tumor contexts. Further, we discuss about their clinical relevance for cancer diagnosis and therapy.

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Section: Mdscs In Prostate Cancermentioning

confidence: 99%

The New Era of Cancer Immunotherapy: Targeting Myeloid-Derived Suppressor Cells to Overcome Immune Evasion

2020

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“…Thus, decreased uPAR expression leads to decreased integrin α 5 β 1 mediated adhesion to the ECM and reduced ERK activation, inducing a dormant state . Although it is not clear whether uPAR plays a role in tumor dormancy in the bone marrow, PC3 prostate cancer cells that were previously grown as subcutaneous tumors in vivo and were able to spontaneously disseminate to the bone marrow expressed elevated levels of uPAR protein by cytokine array in comparison to parental PC3 cells only grown in 2D culture, and uPAR was detected at a higher frequency in bone‐disseminated prostate cancer cells harvested from patients compared to tumor cells found in circulation and was associated with a poor Gleason score …”

Section: Factors Controlling Dormancy or Reactivationmentioning

confidence: 99%

Tumor dormancy in bone

Mayhew¹,

Omokehinde²,

Johnson

2019

Cancer Reports

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Background Bone marrow is a common site of metastasis for a number of tumor types, including breast, prostate, and lung cancer, but the mechanisms controlling tumor dormancy in bone are poorly understood. In breast cancer, while advances in drug development, screening practices, and surgical techniques have dramatically improved survival rates in recent decades, metastatic recurrence in the bone remains common and can develop years or decades after elimination of the primary tumor. Recent Findings It is now understood that tumor cells disseminate to distant metastatic sites at early stages of tumor progression, leaving cancer survivors at a high risk of recurrence. This review will discuss mechanisms of bone lesion development and current theories of how dormant cancer cells behave in bone, as well as a number of processes suspected to be involved in the maintenance of and exit from dormancy in the bone microenvironment. Conclusions The bone is a complex microenvironment with a multitude of cell types and processes. Many of these factors, including angiogenesis, immune surveillance, and hypoxia, are thought to regulate tumor cell entry and exit from dormancy in different bone marrow niches.

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“…Macrophages are of two different polarization types, including the ‘classically’ activated (M1) and the ‘alternatively’ activated (M2) types. Comito’s group reported that increasing infiltration of M2 macrophages was associated with worse pathological characteristics and poor prognosis of PCa [12], while Shi’s group showed that M2 macrophages increased proliferative, migratory and invasive abilities of PCa cells [13], hinting that M2 macrophages may play an important role in PCa progression. M2 macrophages could release some factors and enzymes, such as interleukin-6 (IL-6), interleukin-8 (IL-8), transforming growth factor-β (TGF-β), matrix metallopeptidase-2 (MMP-2), and matrix metallopeptidase-9 (MMP-9) to promote angiogenesis, tumourigenesis, and metastasis [14,15].…”

Section: Introductionmentioning

confidence: 99%

IL-8 Secreted from M2 Macrophages Promoted Prostate Tumorigenesis via STAT3/MALAT1 Pathway

Zheng

Tang

et al. 2018

IJMS

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Prostate cancer (PCa) is a major health problem in males. Metastasis-associated with lung adenocarcinoma transcript-1 (MALAT1), which is overexpressed in PCa tissue, is associated with physiological and pathological conditions of PCa. M2 macrophages are major immune cells abundant in the tumor microenvironment. However, it remains unknown whether M2 macrophages are involved in the effects or not, and molecular mechanisms of MALAT1 on PCa progression have not yet been comprehensively explored. Here we reported that, M2 macrophages (PMA/IL-4 treated THP1) induced MALAT1 expression in PCa cell lines. Knockdown MALAT1 expression level in PCa cell lines inhibited cellular proliferation, invasion, and tumor formation. Further mechanistic dissection revealed that M2 macrophages secreted IL-8 was sufficient to drive up MALAT1 expression level via activating STAT3 signaling pathway. Additional chromatin immunoprecipitation (ChIP) and luciferase reporter assays displayed that STAT3 could bind to the MALAT1 promoter region and transcriptionally stimulate the MALAT1 expression. In summary, our present study identified the IL-8/STAT3/MALAT1 axis as key regulators during prostate tumorigenesis and therefore demonstrated a new mechanism for the MALAT1 transcriptional regulation.

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

Cited by 14 publications

References 43 publications

The New Era of Cancer Immunotherapy: Targeting Myeloid-Derived Suppressor Cells to Overcome Immune Evasion

The New Era of Cancer Immunotherapy: Targeting Myeloid-Derived Suppressor Cells to Overcome Immune Evasion

Tumor dormancy in bone

IL-8 Secreted from M2 Macrophages Promoted Prostate Tumorigenesis via STAT3/MALAT1 Pathway

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