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Prognostic and Predictive Significance of Stromal Fibroblasts and Macrophages in Colon Cancer.

Owusu BY, Vaid M, Kaler P, Klampfer L - Biomark Cancer (2015)

Bottom Line: Cancer cells become reliant on the activity of specific oncogenes and on prosurvival and proliferative signals they receive from the abnormal environment they create and reside in.Because stromal cells are with rare exceptions genetically stable, the tumor microenvironment has emerged as a preferred target for therapeutic drugs.In this review, we discuss the role of stromal fibroblasts and macrophages in colon cancer progression and in the response of colon cancer patients to therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Drug Discovery Division, Southern Research Institute, Birmingham, AL, USA.

ABSTRACT
Colon cancer development and malignant progression are driven by genetic and epigenetic alterations in tumor cells and by factors from the tumor microenvironment. Cancer cells become reliant on the activity of specific oncogenes and on prosurvival and proliferative signals they receive from the abnormal environment they create and reside in. Accordingly, the response to anticancer therapy is determined by genetic and epigenetic changes that are intrinsic to tumor cells and by the factors present in the tumor microenvironment. Recent advances in the understanding of the involvement of the tumor microenvironment in tumor progression and therapeutic response are optimizing the application of prognostic and predictive factors in colon cancer. Moreover, new targets in the tumor microenvironment that are amenable to therapeutic intervention have been identified. Because stromal cells are with rare exceptions genetically stable, the tumor microenvironment has emerged as a preferred target for therapeutic drugs. In this review, we discuss the role of stromal fibroblasts and macrophages in colon cancer progression and in the response of colon cancer patients to therapy.

No MeSH data available.


Related in: MedlinePlus

Interplay between tumor cells and stroma. Fibroblasts and macrophages secrete a variety of soluble factors that trigger oncogenic signaling in tumor cells (Wnt, STAT3, NF-κB), resulting in enhanced proliferation, migration, and resistance to therapy. Note that some factors (eg, TGFβ, IL-6) can be produced by both macrophages and fibroblasts. In turn, tumor cells can produce factors, such as TGFβ, IL-1β, and HGF (indicated by red arrows), that activate stromal cells.
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f1-bic-suppl.1-2015-029: Interplay between tumor cells and stroma. Fibroblasts and macrophages secrete a variety of soluble factors that trigger oncogenic signaling in tumor cells (Wnt, STAT3, NF-κB), resulting in enhanced proliferation, migration, and resistance to therapy. Note that some factors (eg, TGFβ, IL-6) can be produced by both macrophages and fibroblasts. In turn, tumor cells can produce factors, such as TGFβ, IL-1β, and HGF (indicated by red arrows), that activate stromal cells.

Mentions: While therapeutic resistance can develop due to evolution of tumors, accompanied by the acquisition of advantageous genetic and epigenetic changes, the tumor microenvironment plays a major role in therapeutic response. This review is focused on the role of cancer-associated fibroblasts (CAFs) and macrophages in colon cancer progression and the response of colon cancer patients to therapy (Fig. 1). However, by no means do we assume that the contribution of other stromal components, such as T- and B-cells, endothelial cells, and the ECM, to prognosis and therapeutic response of colon cancer patients is marginal. In fact, TNM (T is for T cells and M is for memory) staging in colon cancer has been recently proposed33 and the immunoscore has been introduced for the classification of malignant tumors.34–36


Prognostic and Predictive Significance of Stromal Fibroblasts and Macrophages in Colon Cancer.

Owusu BY, Vaid M, Kaler P, Klampfer L - Biomark Cancer (2015)

Interplay between tumor cells and stroma. Fibroblasts and macrophages secrete a variety of soluble factors that trigger oncogenic signaling in tumor cells (Wnt, STAT3, NF-κB), resulting in enhanced proliferation, migration, and resistance to therapy. Note that some factors (eg, TGFβ, IL-6) can be produced by both macrophages and fibroblasts. In turn, tumor cells can produce factors, such as TGFβ, IL-1β, and HGF (indicated by red arrows), that activate stromal cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4631158&req=5

f1-bic-suppl.1-2015-029: Interplay between tumor cells and stroma. Fibroblasts and macrophages secrete a variety of soluble factors that trigger oncogenic signaling in tumor cells (Wnt, STAT3, NF-κB), resulting in enhanced proliferation, migration, and resistance to therapy. Note that some factors (eg, TGFβ, IL-6) can be produced by both macrophages and fibroblasts. In turn, tumor cells can produce factors, such as TGFβ, IL-1β, and HGF (indicated by red arrows), that activate stromal cells.
Mentions: While therapeutic resistance can develop due to evolution of tumors, accompanied by the acquisition of advantageous genetic and epigenetic changes, the tumor microenvironment plays a major role in therapeutic response. This review is focused on the role of cancer-associated fibroblasts (CAFs) and macrophages in colon cancer progression and the response of colon cancer patients to therapy (Fig. 1). However, by no means do we assume that the contribution of other stromal components, such as T- and B-cells, endothelial cells, and the ECM, to prognosis and therapeutic response of colon cancer patients is marginal. In fact, TNM (T is for T cells and M is for memory) staging in colon cancer has been recently proposed33 and the immunoscore has been introduced for the classification of malignant tumors.34–36

Bottom Line: Cancer cells become reliant on the activity of specific oncogenes and on prosurvival and proliferative signals they receive from the abnormal environment they create and reside in.Because stromal cells are with rare exceptions genetically stable, the tumor microenvironment has emerged as a preferred target for therapeutic drugs.In this review, we discuss the role of stromal fibroblasts and macrophages in colon cancer progression and in the response of colon cancer patients to therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Drug Discovery Division, Southern Research Institute, Birmingham, AL, USA.

ABSTRACT
Colon cancer development and malignant progression are driven by genetic and epigenetic alterations in tumor cells and by factors from the tumor microenvironment. Cancer cells become reliant on the activity of specific oncogenes and on prosurvival and proliferative signals they receive from the abnormal environment they create and reside in. Accordingly, the response to anticancer therapy is determined by genetic and epigenetic changes that are intrinsic to tumor cells and by the factors present in the tumor microenvironment. Recent advances in the understanding of the involvement of the tumor microenvironment in tumor progression and therapeutic response are optimizing the application of prognostic and predictive factors in colon cancer. Moreover, new targets in the tumor microenvironment that are amenable to therapeutic intervention have been identified. Because stromal cells are with rare exceptions genetically stable, the tumor microenvironment has emerged as a preferred target for therapeutic drugs. In this review, we discuss the role of stromal fibroblasts and macrophages in colon cancer progression and in the response of colon cancer patients to therapy.

No MeSH data available.


Related in: MedlinePlus