Dataset Information

Macrophages and Fibroblasts, Key Players in Cancer Chemoresistance.

ABSTRACT: Chemotherapy is routinely used in cancer treatment to eliminate primary and metastatic tumor cells. However, tumors often display or develop resistance to chemotherapy. Mechanisms of chemoresistance can be either tumor cell autonomous or mediated by the tumor surrounding non-malignant cells, also known as stromal cells, which include fibroblasts, immune cells, and cells from the vasculature. Therapies targeting cancer cells have shown limited effectiveness in tumors characterized by a rich tumor stroma. Tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs) are the most abundant non-cancerous cells in the tumor stroma and have emerged as key players in cancer progression, metastasis and resistance to therapies. This review describes the recent advances in our understanding of how CAFs and TAMs confer chemoresistance to tumor cells and discusses the therapeutic opportunities of combining anti-tumor with anti-stromal therapies. The continued elucidation of the mechanisms by which TAMs and CAFs mediate resistance to therapies will allow the development of improved combination treatments for cancer patients.

SUBMITTER: Ireland LV

PROVIDER: S-EPMC6189297 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Macrophages and Fibroblasts, Key Players in Cancer Chemoresistance.

Ireland Lucy V LV Mielgo Ainhoa A

Frontiers in cell and developmental biology 20181009

Chemotherapy is routinely used in cancer treatment to eliminate primary and metastatic tumor cells. However, tumors often display or develop resistance to chemotherapy. Mechanisms of chemoresistance can be either tumor cell autonomous or mediated by the tumor surrounding non-malignant cells, also known as stromal cells, which include fibroblasts, immune cells, and cells from the vasculature. Therapies targeting cancer cells have shown limited effectiveness in tumors characterized by a rich tumor ...[more]

PMID: 30356656

Similar Datasets

Project description:BACKGROUND:Deficient autophagy has been recently implicated as a driver of pulmonary fibrosis, yet bioinformatics approaches to study this cellular process are lacking. Autophagy-related 5 and 7 (ATG5/ATG7) are critical elements of macro-autophagy. However, an alternative ATG5/ATG7-independent macro-autophagy pathway was recently discovered, its regulation being unknown. Using a bioinformatics proteome profiling analysis of ATG7-deficient human fibroblasts, we aimed to identify key microRNA (miR) regulators in autophagy. METHOD:We have generated ATG7-knockout MRC-5 fibroblasts and performed mass spectrometry to generate a large-scale proteomics dataset. We further quantified the interactions between various proteins combining bioinformatics molecular network reconstruction and functional enrichment analysis. The predicted key regulatory miRs were validated via quantitative polymerase chain reaction. RESULTS:The functional enrichment analysis of the 26 deregulated proteins showed decreased cellular trafficking, increased mitophagy and senescence as the major overarching processes in ATG7-deficient lung fibroblasts. The 26 proteins reconstitute a protein interactome of 46 nodes and miR-regulated interactome of 834 nodes. The miR network shows three functional cluster modules around miR-16-5p, miR-17-5p and let-7a related to multiple deregulated proteins. Confirming these results in a biological setting, serially passaged wild-type and autophagy-deficient fibroblasts displayed senescence-dependent expression profiles of miR-16-5p and miR-17-5p. CONCLUSIONS:We have developed a bioinformatics proteome profiling approach that successfully identifies biologically relevant miR regulators from a proteomics dataset of the ATG-7-deficient milieu in lung fibroblasts, and thus may be used to elucidate key molecular players in complex fibrotic pathological processes. The approach is not limited to a specific cell-type and disease, thus highlighting its high relevance in proteome and non-coding RNA research.

Dataset Information

Macrophages and Fibroblasts, Key Players in Cancer Chemoresistance.

Publications

Macrophages and Fibroblasts, Key Players in Cancer Chemoresistance.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets