Mast cells and angiogenesis in gastric carcinoma

Abstract

Previous studies have shown that increased vascularity is associated with haematogenous metastasis and poor prognosis in gastric cancer. The role of mast cells in gastric cancer angiogenesis has not been clarified completely. In this study, we correlated microvascular density and tryptase- and chymase-positive mast cells with histopathological type in gastric cancer. Specimens of primary gastric adenocarcinomas obtained from 30 patients who had undergone curative gastrectomy were investigated immunohistochemically by using anti-CD31 antibody to stain endothelial cells and anti-tryptase and anti-chymase antibodies to stain mast cells. The results showed that stage IV gastric carcinoma has a higher degree of vascularization than other stages and that both tryptase- and chymase-positive mast cells increase in parallel with malignancy grade even if the density of chymase-positive mast cells was significantly lower than the density of tryptase-positive mast cells and is highly correlated with the extent of angiogenesis. This study has demonstrated that mast cell density correlates with angiogenesis and progression of patients with gastric carcinoma. Understanding the mechanisms of gastric cancer angiogenesis provides a basis for a rational approach to the development of an antiangiogenic therapy in patients with this malignancy.

Correlations Between the Density of Tryptase Positive Mast Cells (DMCT) and that of New Blood Vessels (CD105+) in Patients with Gastric Cancer

“…These observations support the idea that mast cells are a negative prognosis factor in gastric tumors, tumoral angiogenesis being the most important pathway that they stimulate [3].…”

“…But the lack of correlation between DMCin and DMVin, demonstrated by this study, may be seen as a sequel of previous studies which have analyzed the mean mast cell density and the mean new vessels density in the gastric wall as a hole, and not on separate, specific areas and depending upon the presence or the absence of Helicobacter pylori infection. Our finding that there are fewer new vessels within the advanced gastric tumors (at least IIB) than in the rest of the stomach wall, correlated with their recognized pro-angiogenic role in the growth and spread of the early stage tumors, as our previous work has demonstrated [3,11], suggests that probably other components of the complex tumoral microenvironment, as well as the rapid growth of advanced tumors, inhibit angiogenesis and limit the density of tumoral new vessels. Low density of tumoral vessels, in contrast with the increased angiogenesis in the rest of the gastric wall is, most probably, another indicator of tumoral aggressiveness, since the tumoral growth is so rapid that exceeds the angiogenesis.…”

“…It associates a poor prognosis due to the fact that up to three fourths of the new cases are diagnosed in late or end stages when the treatment is less effective. Gastric adenocarcinoma growth and distant metastatic spread depend upon tumor angiogenesis [2][3][4].…”

“…Mast cells are both promoters and inhibitors of tumor growth, being the first to infiltrate in the early stage malignancies such as breast, melanoma and colon cancer [8][9]. They may exert either an antitumor role by secreting IL-1 and TNFα; or favor tumor growth due to angiogenesis, break-down of the intercellular matrix and immunosuppression [3,10]. They secrete proteases, such as tryptase and chymase, which act upon extracellular matrix, proteins, and adhesion molecules.…”

Newly Defined Roles of Mast Cells in Surgical Diseases and Surgical Tumors: Review

“…ev re gas trik kar si no ma da di ğer ev re le re kı yas la da ha yük sek dere ce de da mar lan ma gö rül dü ğü nü, ma lig nan si de rece si ile pa ra lel gi den bir trip taz-ve ki maz po zi tif MH ar tı şı nın ol du ğu nu ve bu nun an ji yo ge nez dere ce si ile pa ra lel lik gös ter di ği ni bil dir miş ler dir. 35 Di ğer ta raf tan, stro mal MH in fil tras yo nu nun in va zif me me kan se rin de ba ğım sız prog nos tik belir teç ol du ğu nu bil di ren bir ça lış ma da, c-kit ile 4444 me me kan se ri va ka sı ta ran mış ve MH'nin iyi prog noz işa re ti ol du ğu so nu cu na va rıl mış tır. 36 Böy le ce, li te ra tür de MH-kan ser iliş ki si ne da ir bir çok çe liş ki li so nuç la ra rast lan mak ta dır.…”