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Peritoneal inflammation - A microenvironment for Epithelial Ovarian Cancer (EOC).

Freedman RS, Deavers M, Liu J, Wang E - J Transl Med (2004)

Bottom Line: Preferential involvement of peritoneal structures contributes to the overall poor outcome in EOC patients.These alterations may involve a number of proteins, including cytokines, chemokines, growth factors, either membrane or non-membrane bound, and integrins.These alterations need to be examined and defined as possible prosnosticators and as therapeutic or diagnostic targets.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Gynecologic Oncology, The University of Texas M,D, Anderson Cancer Center, Houston, TX, USA. rfreedma@mdanderson.org

ABSTRACT
Epithelial ovarian cancer (EOC) is a significant cause of cancer related morbidity and mortality in women. Preferential involvement of peritoneal structures contributes to the overall poor outcome in EOC patients. Advances in biotechnology, such as cDNA microarray, are a product of the Human Genome Project and are beginning to provide fresh opportunities to understand the biology of EOC. In particular, it is now possible to examine in depth, at the molecular level, the complex relationship between the tumor itself and its surrounding microenvironment.This review focuses on the anatomy, physiology, and current immunobiologic research of peritoneal structures, and addresses certain potentially useful animal models. Changes in both the inflammatory and non-inflammatory cell compartments, as well as alterations to the extracellular matrix, appear to be signal events that contribute to the remodeling effects of the peritoneal stroma and surface epithelial cells on tumor growth and spread. These alterations may involve a number of proteins, including cytokines, chemokines, growth factors, either membrane or non-membrane bound, and integrins. Interactions between these molecules and molecular structures within the extracellular matrix, such as collagens and the proteoglycans, may contribute to a peritoneal mesothelial surface and stromal environment that is conducive to tumor cell proliferation and invasion. These alterations need to be examined and defined as possible prosnosticators and as therapeutic or diagnostic targets.

No MeSH data available.


Related in: MedlinePlus

Histochemical staining of human ovarian tissue with anti-6-sulfate chondroitin or anti-smooth muscle α-actin antibody. Serial 5-μm sections of paraffin-embedded tumors were stainead with anti-6-sulfate chondroitin (A) or anti-smooth muscle α-actin (B). Arrows point to regions of staining overlap. (Reprinted with permission from Clinical Cancer Research).
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Figure 2: Histochemical staining of human ovarian tissue with anti-6-sulfate chondroitin or anti-smooth muscle α-actin antibody. Serial 5-μm sections of paraffin-embedded tumors were stainead with anti-6-sulfate chondroitin (A) or anti-smooth muscle α-actin (B). Arrows point to regions of staining overlap. (Reprinted with permission from Clinical Cancer Research).

Mentions: Phenotypic and functional characterization of stromal inflammatory and non-inflammatory cell infiltrates will be useful for understanding the biology of metastasis. These infiltrates probably occur following transcapillary migration. In this respect, the chemical composition and dynamics of the extracellular matrix (ECM) are also likely to be important. Thus, chemokines may "stick" to other proteins in the stromal microenvironment, enhancing their chemoattraction and other properties by accumulating at these sites. Proteoglycans, which comprise a protein core, and sulphated or non-sulphated aminoglycan side chains could facilitate this. The proteoglycans include a variety of molecules, such as versican, decorin, hyaluran, and heparan with different side chains. The side chain of decorin can be of the dermatin type or chondroitin SO4 type, each having non-overlapping different functions. We have previously shown that decorin chondroitin SO4 is expressed with myofibroblasts in the adjacent stroma of EOC tissues [49] (Figure 2). A recent paper has shown that endothelial cells stimulated in culture on a collagen type I matrix in the presence of IL6 and IL10 synthesized decorin [50]. This is of particular interest since both IL6 and IL10 are highly expressed in EOC. Chemokines may attach covalently to proteoglycans that express GAG sequences, while retaining their effects on tumor microenvironment cells. This may facilitate their effects locally. In contrast, proteoglycans might also interfere with the binding of activated TGFβ to its receptors.


Peritoneal inflammation - A microenvironment for Epithelial Ovarian Cancer (EOC).

Freedman RS, Deavers M, Liu J, Wang E - J Transl Med (2004)

Histochemical staining of human ovarian tissue with anti-6-sulfate chondroitin or anti-smooth muscle α-actin antibody. Serial 5-μm sections of paraffin-embedded tumors were stainead with anti-6-sulfate chondroitin (A) or anti-smooth muscle α-actin (B). Arrows point to regions of staining overlap. (Reprinted with permission from Clinical Cancer Research).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC459521&req=5

Figure 2: Histochemical staining of human ovarian tissue with anti-6-sulfate chondroitin or anti-smooth muscle α-actin antibody. Serial 5-μm sections of paraffin-embedded tumors were stainead with anti-6-sulfate chondroitin (A) or anti-smooth muscle α-actin (B). Arrows point to regions of staining overlap. (Reprinted with permission from Clinical Cancer Research).
Mentions: Phenotypic and functional characterization of stromal inflammatory and non-inflammatory cell infiltrates will be useful for understanding the biology of metastasis. These infiltrates probably occur following transcapillary migration. In this respect, the chemical composition and dynamics of the extracellular matrix (ECM) are also likely to be important. Thus, chemokines may "stick" to other proteins in the stromal microenvironment, enhancing their chemoattraction and other properties by accumulating at these sites. Proteoglycans, which comprise a protein core, and sulphated or non-sulphated aminoglycan side chains could facilitate this. The proteoglycans include a variety of molecules, such as versican, decorin, hyaluran, and heparan with different side chains. The side chain of decorin can be of the dermatin type or chondroitin SO4 type, each having non-overlapping different functions. We have previously shown that decorin chondroitin SO4 is expressed with myofibroblasts in the adjacent stroma of EOC tissues [49] (Figure 2). A recent paper has shown that endothelial cells stimulated in culture on a collagen type I matrix in the presence of IL6 and IL10 synthesized decorin [50]. This is of particular interest since both IL6 and IL10 are highly expressed in EOC. Chemokines may attach covalently to proteoglycans that express GAG sequences, while retaining their effects on tumor microenvironment cells. This may facilitate their effects locally. In contrast, proteoglycans might also interfere with the binding of activated TGFβ to its receptors.

Bottom Line: Preferential involvement of peritoneal structures contributes to the overall poor outcome in EOC patients.These alterations may involve a number of proteins, including cytokines, chemokines, growth factors, either membrane or non-membrane bound, and integrins.These alterations need to be examined and defined as possible prosnosticators and as therapeutic or diagnostic targets.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Gynecologic Oncology, The University of Texas M,D, Anderson Cancer Center, Houston, TX, USA. rfreedma@mdanderson.org

ABSTRACT
Epithelial ovarian cancer (EOC) is a significant cause of cancer related morbidity and mortality in women. Preferential involvement of peritoneal structures contributes to the overall poor outcome in EOC patients. Advances in biotechnology, such as cDNA microarray, are a product of the Human Genome Project and are beginning to provide fresh opportunities to understand the biology of EOC. In particular, it is now possible to examine in depth, at the molecular level, the complex relationship between the tumor itself and its surrounding microenvironment.This review focuses on the anatomy, physiology, and current immunobiologic research of peritoneal structures, and addresses certain potentially useful animal models. Changes in both the inflammatory and non-inflammatory cell compartments, as well as alterations to the extracellular matrix, appear to be signal events that contribute to the remodeling effects of the peritoneal stroma and surface epithelial cells on tumor growth and spread. These alterations may involve a number of proteins, including cytokines, chemokines, growth factors, either membrane or non-membrane bound, and integrins. Interactions between these molecules and molecular structures within the extracellular matrix, such as collagens and the proteoglycans, may contribute to a peritoneal mesothelial surface and stromal environment that is conducive to tumor cell proliferation and invasion. These alterations need to be examined and defined as possible prosnosticators and as therapeutic or diagnostic targets.

No MeSH data available.


Related in: MedlinePlus