Dataset Information

Brain derived neutrophic factor (BDNF) coordinates lympho-vascular metastasis through a fibroblast-governed paracrine axis in the tumor microenvironment.

ABSTRACT: It has long been known that the tumor microenvironment contributes to the proliferation and survival of neoplasms through the constant interaction with the stromal and immune compartments. In this investigation, we explored the role of cancer-associated fibroblasts (CAFs) in the regulation of the tumor microenvironment in head and neck squamous cell carcinoma (HNSCC) though a complex intercellular BDNF-TrkB signaling system. Our studies show that conditioned media derived from patient-derived CAFs promoted HNSCC cell proliferation, in vitro cell migration, cell invasion and chemotherapy resistance, compared to normal fibroblasts. Furthermore, examination of the in vivo impact of CAF pathophysiology in the tumor microenvironment in animal xenograft models revealed that HNSCC cell lines in combination with CAFs promoted tumor growth and increased incidence of lymphovascular metastasis as compared to injection of tumor cells or CAF cells alone. Using pharmacological and genetic alterations, we mechanistically demonstrate the critical importance of BDNF-TrkB signaling in the tumor microenvironment. These investigations further support the rationale for BDNF/TRKB targeted therapy against in the treatment of HNSCC.

SUBMITTER: Jiffar T

PROVIDER: S-EPMC5617346 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Brain derived neutrophic factor (BDNF) coordinates lympho-vascular metastasis through a fibroblast-governed paracrine axis in the tumor microenvironment.

Jiffar Tilahun T Yilmaz Turker T Lee Junegoo J Miller Yair Y Feng Lei L El-Naggar Adel A Kupferman Michael E ME

Cancer cell & microenvironment 20170710 2

It has long been known that the tumor microenvironment contributes to the proliferation and survival of neoplasms through the constant interaction with the stromal and immune compartments. In this investigation, we explored the role of cancer-associated fibroblasts (CAFs) in the regulation of the tumor microenvironment in head and neck squamous cell carcinoma (HNSCC) though a complex intercellular BDNF-TrkB signaling system. Our studies show that conditioned media derived from patient-derived CA ...[more]

PMID: 28966935

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Project description:BackgroundsPeritoneal invasion in colon cancer is an important prognostic factor. Peritoneal invasion can be objectively identified as periotoneal elastic laminal invasion (ELI) by using elastica stain, and the cancer microenvironment formed by the peritoneal invasion (CMPI) can also be observed. Cases with ELI more frequently show distant metastasis and recurrence. Therefore, CMPI may represent a particular milieu that facilitates tumor progression. Pathological and biological investigations into CMPI may shed light on this possibly distinctive cancer microenvironment.MethodsWe analyzed area-specific tissue microarrays to determine the pathological features of CMPI, and propagated subperitoneal fibroblasts (SPFs) and submucosal fibroblasts (SMFs) from human colonic tissue. Biological characteristics and results of gene expression profile analyses were compared to better understand the peritoneal invasion of colon cancer and how this may form a special microenvironment through the interaction with SPFs. Mouse xenograft tumors, derived by co-injection of cancer cells with either SPFs or SMFs, were established to evaluate their active role on tumor progression and metastasis.ResultsWe found that fibrosis with alpha smooth muscle actin (?-SMA) expression was a significant pathological feature of CMPI. The differences in proliferation and gene expression profile analyses suggested SPFs and SMFs were distinct populations, and that SPFs were characterized by a higher expressions of extracellular matrix (ECM)-associated genes. Furthermore, compared with SMFs, SPFs showed more variable alteration in gene expressions after cancer-cell-conditioned medium stimulation. Gene ontology analysis revealed that SPFs-specific upregulated genes were enriched by actin-binding or contractile-associated genes including ?-SMA encoding ACTA2. Mouse xenograft tumors derived by co-injection of cancer cells with SPFs showed enhancement of tumor growth, metastasis, and capacity for tumor formation compared to those derived from co-injection with cancer cells and SMFs.ConclusionsCMPI is a special microenvironment, and interaction of SPFs and cancer cells within CMPI promote tumor growth and metastasis.

Dataset Information

Brain derived neutrophic factor (BDNF) coordinates lympho-vascular metastasis through a fibroblast-governed paracrine axis in the tumor microenvironment.

Publications

Brain derived neutrophic factor (BDNF) coordinates lympho-vascular metastasis through a fibroblast-governed paracrine axis in the tumor microenvironment.

Similar Datasets

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