Is desmoplasia a protective factor for survival in patients with colorectal carcinoma?

Caporale, A; Vestri, Anna Rita; Benvenuto, Eugenio; Mariotti, Mauro; Cosenza, Umile Michele; Scarpini, M.; Giuliani, Andrea; Mingazzini, P; Angelico, Francesco

doi:10.1016/s1542-3565(04)00674-3

Cited by 22 publications

(23 citation statements)

References 13 publications

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“…For instance, changes in glycosylation and in the repertoire of glycans promote tumor cell invasion and distribution throughout the organism. 5 Processing leading to the modification and accumulation of ECM components in the lamina propria surrounding tumors (desmoplastic reaction) have been associated with both containment of tumor growth and invasion, 6,7 in addition to tumor progression and poor prognosis of colorectal carcinoma (CRC). 8,9 A unifying hypothesis might be that the desmoplastic reaction represents the initial defensive response of the host that then turn out in favor of neoplastic cells.…”

Section: Introductionmentioning

confidence: 99%

Cellular Localization, Invasion, and Turnover Are Differently Influenced by Healthy and Tumor-Derived Extracellular Matrix

Genovese

Zawada

Tosoni

et al. 2014

Tissue Engineering Part A

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The interplay between tumor cells and the microenvironment has been recognized as one of the hallmarks of cancer biology. To assess the role of extracellular matrix (ECM) in the modulation of tissue homeostasis and tumorigenesis, we developed a protocol for the purification of tissue-derived ECM using mucosae from healthy human colon, perilesional area, and colorectal carcinoma (CRC). Matched specimens were collected from the left colon of patients undergoing CRC resection surgery. ECMs were obtained from tissues that were decellularized with hypotonic solutions containing ionic and nonionic detergents, hypertonic solution, and endonuclease in the absence of denaturing agents. Mucosae-derived ECMs maintained distribution and localization of proteins and glycoproteins typical of the original tissues, and showed different three-dimensional (3D) structures among normal versus perilesional and tumor-derived stroma. The three types of ECM differentially regulated the localization and organization of seeded monocytes and cancer cells that were located and organized as in the original tissue. Specifically, healthy, perilesional, and CRC-derived ECMs sustained differentiation and polarization of cancer epithelial cells. In addition, healthy, but not perilesional and CRC-derived ECM constrained invasion of cancer cells. All three ECMs sustained turnover between cell proliferation and death up to 40 days of culture, although each ECM showed different ability in supporting cell proliferation, with tumor > perilesional > healthy-derived ECMs. Healthy-, perilesional-and CRC-derived ECM differently modulated cell homeostasis, spreading in the stroma and turnover between proliferation and death, and equally supported differentiation and polarization of cancer epithelial cells, thus highlighting the contribution of different ECMs modulating some features of tissue homeostasis and tumorigenesis. Moreover, these ECMs provide competent scaffolds useful to assess efficacy of antitumor drugs in a 3D setting that more closely recapitulates the native microenvironment. Further, ECM-based scaffolds may also be beneficial for future studies seeking prognostic and diagnostic stromal markers and targets for antineoplastic drugs.

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Section: Introductionmentioning

confidence: 99%

Cellular Localization, Invasion, and Turnover Are Differently Influenced by Healthy and Tumor-Derived Extracellular Matrix

Genovese

Zawada

Tosoni

et al. 2014

Tissue Engineering Part A

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“…However, desmoplasia has been associated with tumor progression and poor prognosis of colorectal carcinoma, squamous cell carcinoma, breast cancer and scirrhousgastric cancer (Breuninger et al 1997;Halvorsen and Seim 1989;Hasebe et al 2000;Yashiro et al 1996;Miura et al 1993). On the other hand, desmoplastic reaction has been suggested to lead to tumor regression (Martin et al 1987) and to be a protective factor for survival in patients with colorectal carcinoma (Caporale et al 2005). The College of American Pathologists Consensus Statement 1999 states that desmoplasia has not been sufficiently studied to determine its prognostic value for colorectal cancer (Compton et al 2000).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, the physiological implications of this desmoplastic reaction remain to be fully established. Whilst some studies suggest that desmoplastic reaction is an adverse prognostic factor for colorectal cancer (Halvorsen and Seim 1989), others have debated its prognostic value due to insufficient evidence (Compton et al 2000) or see it as a protective factor for survival in patients with colorectal carcinoma (Caporale et al 2005). In this study, we have characterized ECM constituents of the colorectal cancer desmoplastic reaction (collagen types I, III, IV and V and SLRPs decorin, biglycan).…”

Section: Introductionmentioning

confidence: 94%

Colorectal cancer desmoplastic reaction up-regulates collagen synthesis and restricts cancer cell invasion

et al. 2011

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During cancer cell growth many tumors exhibit various grades of desmoplasia, unorganized production of fibrous or connective tissue, composed mainly of collagen fibers and myofibroblasts. The accumulation of an extracellular matrix (ECM) surrounding tumors directly affects cancer cell proliferation, migration and spread; therefore the study of desmoplasia is of vital importance. Stromal fibroblasts surrounding tumors are activated to myofibroblasts and become the primary producers of ECM during desmoplasia. The composition, density and organization of this ECM accumulation play a major role on the influence desmoplasia has upon tumor cells. In this study, we analyzed desmoplasia in vivo in human colorectal carcinoma tissue, detecting an up-regulation of collagen I, collagen IV and collagen V in human colorectal cancer desmoplastic reaction. These components were then analyzed in vitro co-cultivating colorectal cancer cells (Caco-2 and HCT116) and fibroblasts utilizing various co-culture techniques. Our findings demonstrate that direct cell-cell contact between fibroblasts and colorectal cancer cells evokes an increase in ECM density, composed of unorganized collagens (I, III, IV and V) and proteoglycans (biglycan, fibromodulin, perlecan and versican). The desmoplastic collagen fibers were thick, with an altered orientation, as well as deposited as bundles. This increased ECM density inhibited the migration and invasion of the colorectal tumor cells in both 2D and 3D co-culture systems. Therefore this study sheds light on a possible restricting role desmoplasia could play in colorectal cancer invasion.

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“…It is not known whether it gives to the tumoral cells a growth advantage or it is a reaction of the host to inhibit cancer cell progression. Caporale et al [25], studying desmoplasia in colorectal carcinoma, concluded that it may prevent cancer invasiveness by building a barrier against tumor diffusion. In salivary gland tumors, Sobral et al [26] showed greater desmoplasia in low-grade mucoepidermoid carcinoma when compared with high-grade mucoepidermoid carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Desmoplasia in Different Degrees of Invasion of Carcinoma Ex-Pleomorphic Adenoma

Araújo

Furuse

Cury

et al. 2007

Head and Neck Pathol

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Stroma desmoplasia was studied by immunohistochemistry for alpha-smooth muscle actin (alpha-SMA) in 17 instances of carcinoma ex-pleomorphic adenoma (CXPA) classified according to the presence of epithelial and myoepithelial cells and the degree of invasion: intracapsular, minimally and frankly invasive carcinoma. In "resident" pleomorphic adenoma, no desmoplasia was detected. In invasive areas of the intracapsular type of CXPA with only an epithelial component, desmoplasia started to be revealed by the presence of myofibroblasts close to the capsule. In the minimally invasive type, myofibroblasts were seen in the septum between islands of malignant cells and in focal peripheral areas of the tumor interpreted as the actual front of invasion. In the frankly invasive type of CXPA showing large blocks of cells, intense desmoplasia was seen, also separating the tumor cells from the neighboring normal tissue. In tumors with cords and/or small nests of cells, desmoplasia was very slight. In the invasive type of CXPA with a myoepithelial component, alpha-SMA expression was seen in the septum between the islands of cells. The expression was less intense and not present in all areas of the stroma. In CXPA with epithelial and myoepithelial cells, myofibroblasts were rarely seen in the septum separating sheets of cells. Thus, we may deduce that the presence of desmoplasia parallels the capacity of invasion of CXPA by epithelial cells, being minimum in the intracapsular and minimally invasive type of CXPA and increasing as the tumor becomes frankly invasive. Furthermore, we may also conclude that in CXPA with a myoepithelial component, desmoplasia is very rare.

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Is desmoplasia a protective factor for survival in patients with colorectal carcinoma?

Cited by 22 publications

References 13 publications

Cellular Localization, Invasion, and Turnover Are Differently Influenced by Healthy and Tumor-Derived Extracellular Matrix

Cellular Localization, Invasion, and Turnover Are Differently Influenced by Healthy and Tumor-Derived Extracellular Matrix

Colorectal cancer desmoplastic reaction up-regulates collagen synthesis and restricts cancer cell invasion

Desmoplasia in Different Degrees of Invasion of Carcinoma Ex-Pleomorphic Adenoma

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