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Eur J Cardiothorac Surg 2006;29:638-639
© 2006 Elsevier Science NL

Letter to the Editor

The role of mast cell and mast cell subtypes (MC_T and MC_CT) in tumor angiogenesis

Department of Pediatrics, Division of Allergy/Immunology, Louisiana State University Health Sciences Center, 1542 Tulane Avenue, T8-1, New Orleans, LA, United States

Received 13 December 2005; accepted 10 January 2006.

^_* Tel.: +1 504 568 2578; fax:+1 504 568 7598. (Email: ozdemir_oner{at}hotmail.com; oner.ozdemir.md{at}gmail.com).

Key Words: Mast cell • MC_T • MC_CT • Angiogenesis • Tumor development • Mast cell-mediated cytotoxicity

I read the article by Ibaraki et al. [1] describing ‘The relationship of tryptase- and chymase-positive mast cells to angiogenesis in stage I non-small cell lung cancer’ with great interest. Here, I discuss my concerns about mast cell (MC)-induced tumor angiogenesis with our in vitro findings, showing anti-tumor effect of MCs [2].

Some hold macrophage/tumor/endothelial progenitor or stromal cells responsible from neoplastic angiogenesis in non-small cell lung cancer (NSCLC). Is MC really an active player? Increased MC density (MCD) might be a reflection of generalized inflammatory reaction, e.g., in breast cancer. Could any MC subtype have a specific role? Increased MCD may not associate with proportional changes of subtypes, which could be modified by their environment. In contrast with this study, no proportional change was detected in hepatocellular carcinoma. Authors demonstrated MC_CT increase at the border zone, contrary to cervix/breast carcinoma. There are also few data suggesting increased MC_CT as worse prognostic indicator, e.g., in lip cancer, as opposed to renal/colorectal carcinoma. Chymase also induces apoptosis in endothelial cells and the accumulation of tumor-associated macrophages indicating MC cytotoxicity besides its effect on matrix metalloproteinase-9, similar to our findings [2].

Increased MCD is neither always associated with bad prognosis nor angiogenesis. It can also indicate a better survival such as in soft tissue sarcomas. Earlier studies showed increased tumor development in MC-deficient mice as well as no significant difference between MC-deficient and sufficient mice for the angiogenesis. Recent studies also found no significant association between angiogenesis and MCD such as in ovarian cancer, even with NSCLC [3]. If MC always induces angiogenesis, how do authors explain the lack of correlation between angiogenesis and systemic MC diseases.

Although it is hard to explain these conflicting results, they may be due to variations in the timing of the study, tumor types as well as methodologies. No standardized scheme is yet available to assess the angiogenesis. Heterogeneity of endothelial cell marker expressions even in a tumor is well known. CD105, proliferation marker, proved to be superior to pan-endothelial marker (CD34) in NSCLC [4]. Utilizing these markers facilitates the vascular status estimation but may not show the angiogenic status. Some tumors are vascularized without significant angiogenesis by vascular mimicry. Authors did not mention microvessel density (MVD) of the normal region in this study. Also, since given standard deviations are so high, the assumed MVD increase raises a suspicion. Moreover, mean MVD was reported to be 80 in NSCLC using same methodologies [5]. Choosing an evaluation zone in a tumor stroma is another dilemma. Recently, increased tumor islet MCD in NSCLC noticed as favorable.

Finally, anti-angiogenic effect of tranilast occurs not by simply MC stabilization rather via its overall inhibiting effect on macrophage cytokine release, fibroblast, and smooth muscle proliferation. Only observing increased MCD in a tumor with bad/good prognosis on pathological specimens seems to be far behind to explain the role of MCs.

References

1. Ibaraki T, Muramatsu M, Takai S, Jin D, Maruyama H, Orino T, Katsumata T, Miyazaki M. The relationship of tryptase- and chymase-positive mast cells to angiogenesis in stage I non-small cell lung cancer. Eur J Cardiothorac Surg 2005;28(4):617-621.[Abstract/Free Full Text]
2. Ozdemir O, Ravindranath Y, Savasan S. Short term mast cell natural cell-mediated cytotoxicity. Ann Allergy Asthma Immunol 2004;94(1):186-187.
3. Chandrachud LM, Pendleton N, Chisholm DM, Horan MA, Schor AM. Relationship between vascularity, age and survival in non-small-cell lung cancer. Br J Cancer 1997;76(10):1367-1375.[Medline]
4. Tanaka F, Otake Y, Yanagihara K, Kawano Y, Miyahara R, Li M, Otake Y, Wada H. Evaluation of angiogenesis in non-small cell lung cancer: comparison between anti-CD34 antibody and anti-CD105 antibody. Clin Cancer Res 2001;7(11):3410-3415.[Abstract/Free Full Text]
5. Shibusa T, Shijubo N, Abe S. Tumor angiogenesis and vascular endothelial growth factor expression in stage I lung adenocarcinoma. Clin Cancer Res 1998;4(6):1483-1487.[Abstract]

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ozdemir, O. Search for Related Content PubMed PubMed Citation Articles by Ozdemir, O. Related Collections Lung - cancer