A Digest on the Role of the Tumor Microenvironment in Gastrointestinal Cancers

Augsten, Martin; Hägglöf, Christina; Peña, Cristina; Östman, Arne

doi:10.1007/s12307-010-0040-9

Cited by 34 publications

(29 citation statements)

References 135 publications

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“…22 The stromas of tumors provide a large number of factors that enhance propagation and metastases of tumors and that probably vary with the stromas of different cancers. 23 The results here suggest that STC1 secreted by MSC-like cells in tumor stroma plays a critical role in enhancing the Warburg effect and making tumors resistant to ROS. Therefore blocking antibodies or antagonists to STC1 may be attractive candidates as an adjunct therapy for γ-radiation and other therapies that increase ROS.…”

Section: Discussionmentioning

confidence: 65%

Mesenchymal Stromal Cells Protect Cancer Cells From ROS-induced Apoptosis and Enhance the Warburg Effect by Secreting STC1

et al. 2012

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Previous studies have demonstrated that mesenchymal stromal cells (MSCs) enhance cell survival through upregulation and secretion of stanniocalcin-1 (STC1). This study shows that MSC-derived STC1 promotes survival of lung cancer cells by uncoupling oxidative phosphorylation, reducing intracellular reactive oxygen species (ROS), and shifting metabolism towards a more glycolytic metabolic profile. MSC-derived STC1 upregulated uncoupling protein 2 (UCP2) in injured A549 cells in an STC1-dependent manner. Knockdown of UCP2 reduced the ability of MSCs and recombinant STC1 (rSTC1) to reduce cell death in the A549 population. rSTC1-treated A549 cells displayed decreased levels of ROS, mitochondrial membrane potential (MMP), and increased lactate production, all of which were dependent on the upregulation of UCP2. Our data suggest that MSCs can promote cell survival by regulating mitochondrial respiration via STC1.

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Section: Discussionmentioning

confidence: 65%

Mesenchymal Stromal Cells Protect Cancer Cells From ROS-induced Apoptosis and Enhance the Warburg Effect by Secreting STC1

et al. 2012

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“…However, CAFs comprise a heterogeneous population of cells and are derived from different sources (13). The CAF heterogeneity observed may reflect the variation of CAF involvement in cancer progression.…”

Section: Introductionmentioning

confidence: 99%

Functional Heterogeneity of Cancer-Associated Fibroblasts from Human Colon Tumors Shows Specific Prognostic Gene Expression Signature

Herrera

Islam

Herrera

et al. 2013

Clinical Cancer Research

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149

124

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Purpose: Cancer-associated fibroblasts (CAF) actively participate in reciprocal communication with tumor cells and with other cell types in the microenvironment, contributing to a tumor-permissive neighborhood and promoting tumor progression. The aim of this study is the characterization of how CAFs from primary human colon tumors promote migration of colon cancer cells. Experimental design: Primary CAF cultures from 15 primary human colon tumors were established. Their enrichment in CAFs was evaluated by the expression of various epithelial and myofibroblast specific markers. Coculture assays of primary CAFs with different colon tumor cells were performed to evaluate promigratory CAF-derived effects on cancer cells. Gene expression profiles were developed to further investigate CAF characteristics. Results: Coculture assays showed significant differences in fibroblast-derived paracrine promigratory effects on cancer cells. Moreover, the association between CAFs' promigratory effects on cancer cells and classic fibroblast activation or stemness markers was observed. CAF gene expression profiles were analyzed by microarray to identify deregulated genes in different promigratory CAFs. The gene expression signature, derived from the most protumorogenic CAFs, was identified. Interestingly, this “CAF signature” showed a remarkable prognostic value for the clinical outcome of patients with colon cancer. Moreover, this prognostic value was validated in an independent series of 142 patients with colon cancer, by quantitative real-time PCR (qRT-PCR), with a set of four genes included in the “CAF signature.” Conclusions: In summary, these studies show for the first time the heterogeneity of primary CAFs' effect on colon cancer cell migration. A CAF gene expression signature able to classify patients with colon cancer into high- and low-risk groups was identified. Clin Cancer Res; 19(21); 5914–26. ©2013 AACR.

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“…The conditions in the tumor microenvironment such as hypoxia, increased glycolysis, and other metabolic changes are conducive for metastasis [3]. While solid tumors are rich in quiescent cells, developing tumors contain proliferating cells [4, 5]. Additionally, the tissue architecture of tumors shows a great variation from its normal counterparts in tissue integrity and exhibit differential genetic programming [6-8].…”

Section: Introductionmentioning

confidence: 99%

Tumor microsomal metabolism of the food toxicant, benzo(a)pyrene, in Apc Min mouse model of colon cancer

et al. 2012

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The present study was conducted to investigate whether colon tumors were capable of metabolizing benzo (a)pyrene (BaP), and fluoranthene (FLA), two toxicants that belong to the polycyclic aromatic hydrocarbon family of compounds. Microsomes were isolated from the colon tumors of ApcMin mice that received subchronic doses of 50 μg/kg BaP and incubated with either BaP or FLA (3 μM each) alone or in combination and appropriate control groups that received nothing. Subsequent to incubation, samples were extracted with ethyl acetate and analyzed for BaP and FLA metabolites by reverse-phase HPLC equipped with fluorescence detection. Microsomes from tumor tissues were found to metabolize BaP to a greater extent than those from the non-tumor tissues. The rate of BaP metabolism (picomoles of metabolite per minute per milligram of protein) was found to be more when microsomes from BaP-pretreated mice were exposed to BaP alone and FLA in combination with BaP, compared to controls. The microsomes from BaP-preexposed mice generated greater proportion of BaP 7,8-diol and BaP 3,6- and 6,12-diones compared to other experimental groups. Additionally, microsomes from BaP-pretreated mice produced greater proportion of FLA 2, 3-diol and 2, 3 D FLA when microsomes were incubated with FLA alone or a combination of BaP and FLA. Our studies revealed that the tumor microsomes were competent to metabolize BaP and FLA either singly or in combination. The biotransformation of BaP and FLA as a consequence of prior and simultaneous exposure to BaP may influence the growth of tumors. Our findings may have relevance to human long-term dietary intake of these toxicants and the consequent acceleration of the colon carcinogenesis process.

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A Digest on the Role of the Tumor Microenvironment in Gastrointestinal Cancers

Cited by 34 publications

References 135 publications

Mesenchymal Stromal Cells Protect Cancer Cells From ROS-induced Apoptosis and Enhance the Warburg Effect by Secreting STC1

Mesenchymal Stromal Cells Protect Cancer Cells From ROS-induced Apoptosis and Enhance the Warburg Effect by Secreting STC1

Functional Heterogeneity of Cancer-Associated Fibroblasts from Human Colon Tumors Shows Specific Prognostic Gene Expression Signature

Tumor microsomal metabolism of the food toxicant, benzo(a)pyrene, in Apc Min mouse model of colon cancer

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