Catabolic cancer-associated fibroblasts transfer energy and biomass to anabolic cancer cells, fueling tumor growth

2014 ◽  
Vol 25 ◽  
pp. 47-60 ◽  
Author(s):  
Ubaldo E. Martinez-Outschoorn ◽  
Michael P. Lisanti ◽  
Federica Sotgia
Keyword(s):  
Tumor Growth ◽  
Cancer Cells ◽  
Cancer Associated Fibroblasts ◽  
Transfer Energy

scholarly journals Cancer-Associated Fibroblasts Promote Migration and Invasion of Non-Small Cell Lung Cancer Cells via miR-101-3p Mediated VEGFA Secretion and AKT/eNOS Pathway

2021 ◽  
Vol 9 ◽  
Author(s):  
Xueru Guo ◽  
Mengmeng Chen ◽  
Limin Cao ◽  
Yiming Hu ◽  
Xueqin Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Growth ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Small Cell ◽  
Lung Cancer Cells ◽  
Migration And Invasion ◽  
Cancer Associated Fibroblasts ◽  
Small Cell Lung ◽  
Promoting Effect

Cancer-associated fibroblasts (CAFs) are major component of tumor microenvironment (TME), which plays crucial roles in tumor growth, invasion and metastasis; however, the underling mechanism is not fully elucidated. Despite many studies are focused on the tumor promoting effect of CAFs-derived cytokines, the upstream regulators of cytokine release in CAFs is largely unknown. Here we found that miR-101-3p was downregulated in primary lung cancer-associated CAFs compared to normal fibroblasts (NFs). Ectopic overexpression of miR-101-3p suppressed CAFs activation, and abrogated the promoting effect of CAFs on migration and invasion of non-small cell lung cancer cells (NSCLC), through attenuating CAFs’ effect on epithelial mesenchymal transition (EMT) process, metastasis-related genes (MMP9, TWIST1) and AKT/endothelial nitric oxide synthase (eNOS) signaling pathway. Further study indicated that vascular endothelial growth factor A (VEGFA) was a novel target of miR-101-3p, and CAFs-derived VEGFA mediated the effect of miR-101-3p on migration and invasion of lung cancer cells, demonstrated by using recombinant VEGFA and VEGFA neutralizing antibody. Interestingly, the analysis of the Cancer Genome Atlas (TCGA) database revealed that lung cancer tissues expressed lower level of miR-101-3p than non-cancerous tissues, and low/medium-expression of miR-101-3p was associated with poor overall survival (OS) rate. Moreover, the mouse xenograft experiment also showed that CAFs accelerated tumor growth whereas miR-101-3p diminished CAFs’ effect. These findings revealed a novel mechanism that CAFs facilitated lung cancer metastasis potential via miR-101-3p/VEGFA/AKT signaling pathway, suggesting miR-101-3p as a potential candidate for metastasis therapy.

scholarly journals Altered p53 functionality in cancer-associated fibroblasts contributes to their cancer-supporting features

2018 ◽  
Vol 115 (25) ◽  
pp. 6410-6415 ◽  
Author(s):  
Sharathchandra Arandkar ◽  
Noa Furth ◽  
Yair Elisha ◽  
Nishanth Belugali Nataraj ◽  
Heiko van der Kuip ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Migration And Invasion ◽  
Cancer Associated Fibroblasts ◽  
Tumor Cell Migration ◽  
Promote Tumor Growth ◽  
Transcriptional Rewiring ◽  
A Cell

Within the tumor microenvironment, cancer cells coexist with noncancerous adjacent cells that constitute the tumor microenvironment and impact tumor growth through diverse mechanisms. In particular, cancer-associated fibroblasts (CAFs) promote tumor progression in multiple ways. Earlier studies have revealed that in normal fibroblasts (NFs), p53 plays a cell nonautonomous tumor-suppressive role to restrict tumor growth. We now wished to investigate the role of p53 in CAFs. Remarkably, we found that the transcriptional program supported by p53 is altered substantially in CAFs relative to NFs. In agreement, the p53-dependent secretome is also altered in CAFs. This transcriptional rewiring renders p53 a significant contributor to the distinct intrinsic features of CAFs, as well as promotes tumor cell migration and invasion in culture. Concordantly, the ability of CAFs to promote tumor growth in mice is greatly compromised by depletion of their endogenous p53. Furthermore, cocultivation of NFs with cancer cells renders their p53-dependent transcriptome partially more similar to that of CAFs. Our findings raise the intriguing possibility that tumor progression may entail a nonmutational conversion (“education”) of stromal p53, from tumor suppressive to tumor supportive.

scholarly journals Cancer associated fibroblasts transfer lipids and proteins to cancer cells through cargo vesicles supporting tumor growth

2015 ◽  
Vol 1853 (12) ◽  
pp. 3211-3223 ◽  
Author(s):  
Alice Santi ◽  
Anna Caselli ◽  
Francesco Ranaldi ◽  
Paolo Paoli ◽  
Camilla Mugnaioni ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Cancer Cells ◽  
Cancer Associated Fibroblasts

scholarly journals Cancer: An Oxidative Crosstalk between Solid Tumor Cells and Cancer Associated Fibroblasts

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Alessandro Arcucci ◽  
Maria Rosaria Ruocco ◽  
Giuseppina Granato ◽  
Anna Maria Sacco ◽  
Stefania Montagnani
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Critical Role ◽  
Metabolic Reprogramming ◽  
Antioxidant Systems ◽  
Activation Process ◽  
Cancer Associated Fibroblasts

Redox balance is associated with the regulation of several cell signalling pathways and functions. In fact, under physiological conditions, cells maintain a balance between oxidant and antioxidant systems, and reactive oxygen species (ROS) can act as second messengers to regulate cell proliferation, cell death, and other physiological processes. Cancer tissues usually contain higher levels of ROS than normal tissues, and this ROS overproduction is associated with tumor development. Neoplastic tissues are very heterogeneous systems, composed of tumor cells and microenvironment that has a critical role in tumor progression. Cancer associated fibroblasts (CAFs) represent the main cell type of tumor microenvironment, and they contribute to tumor growth by undergoing an irreversible activation process. It is known that ROS can be transferred from cancer cells to fibroblasts. In particular, ROS affect the behaviour of CAFs by promoting the conversion of fibroblasts to myofibroblasts that support tumor progression and dissemination. Furthermore, the wrecking of redox homeostasis in cancer cells and tumor microenvironment induces a metabolic reprogramming in tumor cells and cancer associated fibroblasts, giving advantage to cancer growth. This review describes the role of ROS in tumor growth, by focusing on CAFs activation and metabolic interactions between cancer cells and stromal fibroblasts.

scholarly journals CD63 + Cancer‐Associated Fibroblasts Confer Tamoxifen Resistance to Breast Cancer Cells through Exosomal miR‐22

2020 ◽  
Vol 7 (21) ◽  
pp. 2002518
Author(s):  
Yuan Gao ◽  
Xiaoju Li ◽  
Cheng Zeng ◽  
Chenlin Liu ◽  
Qiang Hao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Tamoxifen Resistance ◽  
Cancer Associated Fibroblasts
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