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Immune suppressive signaling regulated by latent transforming growth factor beta binding protein 1 promotes metastasis in cervical cancer.

ABSTRACT: Although metastasis is the major cause of death in cervical cancer, the mechanism of metastasis is still unclear. The mRNA expression and protein level of latent transforming growth factor beta binding protein 1 (LTBP1) were detected in tumor tissues and paracancerous tissues from in-house samples. Cell proliferation, cell cycle, migration, and in vivo metastasis were determined after LTBP1 was knocked down. Then, 13 drugs were screened, and the changes in cell apoptosis and proliferation and tumor metastasis were detected after drug treatment in shRNA cells. In our in-house samples, LTBP1 was lowly expressed in cervical cancer tissues. After LTBP1 knockdown, cell proliferation was increased, and the ability of in vitro migration and in vivo metastasis was enhanced. At the same time, the proportion of myeloid derived suppressor cells (MDSC) in situ increased, the proportion of T cells decreased, and transforming growth factor beta-1 (TGFβ1) signaling was activated. After carboplatin treatment, LTBP1 shRNA cell line apoptosis increased, metastasis in vivo was limited, and the proportion of MDSC in situ decreased. LTBP1 was lowly expressed in cervical cancer, and the inhibition of LTBP1 can improve the malignant degree of the tumor, and this process can be blocked by carboplatin.

SUBMITTER: Gu H

PROVIDER: S-EPMC9828866 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Immune suppressive signaling regulated by latent transforming growth factor beta binding protein 1 promotes metastasis in cervical cancer.

Gu Haiyan H Wang Wei W Sun Changdong C Ding Li L Li Li L Shu Peng P Xu Jun J

Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica 20230109

Although metastasis is the major cause of death in cervical cancer, the mechanism of metastasis is still unclear. The mRNA expression and protein level of latent transforming growth factor beta binding protein 1 (LTBP1) were detected in tumor tissues and paracancerous tissues from in-house samples. Cell proliferation, cell cycle, migration, and in vivo metastasis were determined after LTBP1 was knocked down. Then, 13 drugs were screened, and the changes in cell apoptosis and proliferation and tu ...[more]

PMID: 36629522

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Project description:ObjectiveLaminin subunit Beta-1 (LAMB1), a component of the extracellular matrix, has been reported to be implicated in the development and progression of cancer. However, the role of LAMB1 in Nasopharyngeal Carcinoma (NPC) remains unknown.MethodsThree NPC datasets were utilized to identify LAMB1 as a targeted gene. The correlation between LAMB1 expression and clinical characteristics, prognosis was explored. KEGG and GO enrichment analyses were conducted to investigate LAMB1's functions in NPC. The CIBERSORT, xCell, MCPCOUNTER, and EPIC methods were used to assess the Cancer-Associated Fibroblasts (CAFs) and immune cells infiltration. We predicted LAMB1's effect on treatment using TIDE, CTRP, and CellMine databases. Finally, Western blot, CCK-8, Transwell, and Wound scratch were employed to validate LAMB1's effect on NPC cells.ResultsLAMB1 was highly expressed in NPC. High-expression LAMB1 was correlated with poorer progression-free survival and impeded the infiltration of CD4+ T-cells, CD8+ T-cells and dendritic cells. It also diminished the expression of HLA and suppressed T-cells stimulation. Differential expressed cytokines and involved pathways were divergent across different level of fibroblasts infiltration. At high level of fibroblasts, LAMB1 indirectly inhibited immune cells by remolding extracellular matrix. But at low level of fibroblasts, LAMB1 directly suppressed immune response. Tumors with high LAMB1 level had weak responses to immunotherapy. In vitro experiment, LAMB1 significantly suppressed HLA-1 and enhanced the proliferation, migration, and invasion capabilities of NPC cells.ConclusionHigh expression of LAMB1 is significantly associated with an immune-suppressive tumor microenvironment in NPC. LAMB1 enhances the proliferation, migration and invasion of NPC cells. These findings suggest that LAMB1 may serve as a prognostic biomarker for predicting NPC progression and a potential therapeutic target to enhance the efficacy of existing immunotherapies.Level of evidence: 3

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Immune suppressive signaling regulated by latent transforming growth factor beta binding protein 1 promotes metastasis in cervical cancer.

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Immune suppressive signaling regulated by latent transforming growth factor beta binding protein 1 promotes metastasis in cervical cancer.

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