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Year : 2015  |  Volume : 11  |  Issue : 4  |  Page : 1041

The role of mast cell density in tumor-associated angiogenesis and survival of squamous cell carcinoma of the lung

Department of Pediatrics, Division of Allergy and Immunology, Research and Training Hospital of Sakarya University, Adapazarı, Sakarya, Turkey

Date of Web Publication15-Feb-2016

Correspondence Address:
Oner Ozdemir
The role of mast cell density in tumor, Research and Training Hospital of Sakarya University, Faculty of Medicine, Sakarya University, Adnan Menderes Cad, Sağlık Sok. No: 195, Adapazarı, Sakarya
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-1482.140983

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How to cite this article:
Ozdemir O. The role of mast cell density in tumor-associated angiogenesis and survival of squamous cell carcinoma of the lung. J Can Res Ther 2015;11:1041

How to cite this URL:
Ozdemir O. The role of mast cell density in tumor-associated angiogenesis and survival of squamous cell carcinoma of the lung. J Can Res Ther [serial online] 2015 [cited 2020 Feb 25];11:1041. Available from: http://www.cancerjournal.net/text.asp?2015/11/4/1041/140983


I read an article by Ullah et al. titled to “Angiogenesis and mast cell density (MCD) as predictors of patient survival in squamous cell carcinoma of the lung (SCCL)” with great interest.[1] Their study showed that angiogenesis and MCD are positively correlated however; only high microvascular density (MVD) is significantly associated with decreased survival. We are especially concerned about their idea of using anti-mast cell (MC) agents as an anticancer drug in SCCL treatment, due to the thought of MC as an essential pro-angiogenic element. Since the role of MCs in the tumor tissue has been very controversial so far, this comprehension needs further clarification. Furthermore, in contrast to their conclusion, we have recently demonstrated human MC-mediated cytotoxicity against different human tumor cells in vitro.[2]

There are several conclusions that I have found them very hard to understand. For example: If there was a negative correlation between MVD and grade, and high MVD was noticed in well-differentiated tumor; how high MVD would be associated with poor survival? Such as in advanced ovarian cancer, high MVD possibly contributed to a better chemotherapy response and the overall better survival. Another puzzling conclusion is that although high MCD were positively correlated with angiogenesis, early stage/well-differentiated tumors and negatively correlated with grade; they thought MCs can serve as a novel therapeutic target. Our interpretation is that MCD may be pro-angiogenic, but it might have antitumor effects thru angiogenesis. Another conflicting assumption is that, after finding no direct correlation between survival and MCD, how can one advocate on the prognostic significance of MC phenotypes in SCCL? Nonetheless, higher MC tryptase-chymase phenotype was even found to be a good prognostic predictor in lung adenocarcinoma and SCCL.[3]

Mast cells mediating the angiogenesis may not necessarily cause tumor growth, but they can inhibit tumor progression. Increased tumor islet MCD in SCCL noticed as favorable. The expression of tumor necrosis factor-α by MCs in the tumor islets of SCCL was associated with improved survival.[4] Some hold macrophages and other stromal cells responsible from angiogenesis in SCCL. The numbers of macrophages/CD8+ - T cells in tumor stroma were useful for predicting the prognosis of SCCL.[5]

Vessels in five high-power fields (×400 magnifications) were counted, and mean MVD was found to be 12 ± 4. In other studies, the number of MCs per 10 fields at a magnification of ×200 or ×250 was counted. The median MVD count is ranging from 20 to 222 ± 120 in SCCL using the same methodologies.[3],[4],[5],[6] After the microvessel count was determined, the microvessels were further generally stained with Alcian blue and safranin O to show areas of MC infiltration, instead of just tolouidine blue. Moreover, common pan-endothelial cell marker (CD34) for detection of MVD are nonspecific and may not reflect the real angiogenic status in some tumors vascularizing without significant angiogenesis. Those markers do not discriminate new from old microvessels. Furthermore, CD105, a proliferation marker, was proved to be superior to pan-endothelial markers in SCCL.[6]

Finally; MCs are considered as a new target for the treatment of tumors through the selective inhibition of neoangiogenesis. Inhibiting MC function may regress tumor growth, but lead to dangerous consequences e.g, highly malignant neuroendocrine cancer development.[7] In the age of targeted therapy, studies of the targeting MCs' role in cancer should be further elucidated.

 > References Top

Ullah E, Nagi AH, Ashraf M. Angiogenesis and mast cell density as predictors of patient survival in squamous cell carcinoma of lung. J Cancer Res Ther 2013;9:701-5.  Back to cited text no. 1
Ozdemir O. Flow cytometric mast cell-mediated cytotoxicity assay: A three-color flow cytometric approach using monoclonal antibody staining with annexin V/propidium iodide co-labeling to assess human mast cell-mediated cytotoxicity by fluorosphere-adjusted counts. J Immunol Methods 2011;365:166-73.  Back to cited text no. 2
Nagata M, Shijubo N, Walls AF, Ichimiya S, Abe S, Sato N. Chymase-positive mast cells in small sized adenocarcinoma of the lung. Virchows Arch 2003;443:565-73.  Back to cited text no. 3
Ohri CM, Shikotra A, Green RH, Waller DA, Bradding P. Tumour necrosis factor-alpha expression in tumour islets confers a survival advantage in non-small cell lung cancer. BMC Cancer 2010;10:323.  Back to cited text no. 4
Kawai O, Ishii G, Kubota K, Murata Y, Naito Y, Mizuno T, et al. Predominant infiltration of macrophages and CD8(+) T Cells in cancer nests is a significant predictor of survival in stage IV nonsmall cell lung cancer. Cancer 2008;113:1387-95.  Back to cited text no. 5
Tanaka F, Otake Y, Yanagihara K, Kawano Y, Miyahara R, Li M, et al. Evaluation of angiogenesis in non-small cell lung cancer: Comparison between anti-CD34 antibody and anti-CD105 antibody. Clin Cancer Res 2001;7:3410-5.  Back to cited text no. 6
Pittoni P, Tripodo C, Piconese S, Mauri G, Parenza M, Rigoni A, et al. Mast cell targeting hampers prostate adenocarcinoma development but promotes the occurrence of highly malignant neuroendocrine cancers. Cancer Res 2011;71:5987-97.  Back to cited text no. 7


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