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

Letter to the Editor

Reply to Ozdemir

Shinji Takai * , Toshihiko Ibaraki, Michiko Muramatsu, Mizuo Miyazaki

Department of Pharmacology, Osaka Medical College, Takatsuki City, Osaka 569-8686, Japan

Received 6 January 2006; accepted 10 January 2006.

* Corresponding author. Tel.: +81 726 84 7292; fax: +81 726 84 6518. (Email: pha010{at}art.osaka-med.ac.jp).

Key Words: Angiogenesis • Lung cancer • Chymase • Mast cells

The fact that mast cells are present in large numbers around cancers is well known; further, mast cells contain many angiogenesis factors. Many reports have indicated the involvement of mast cells in cancer angiogenesis. In our report, we demonstrated that chymase-positive mast cells are involved in angiogenesis around stage-1 non-small cell lung cancers suggesting the possibility that chymase is involved in cancer angiogenesis [1]. However, Ozdemir et al. [2] found that mast cells which were differentiated from bone marrow mononuclear cells inhibited tumor cell growth in vitro and concluded that mast cells have antitumor activities.

Although Ozdemir cited reports that found no tumor suppression in mast cell-deficient mice, many reports, to the contrary, documenting tumor suppression in mast cell-deficient mice have been made. Also, he mentioned reports that, unlike our study, found no correlation between the number of vessels and the concentration of mast cells. These differences in outcome may suggest that the roles of mast cells differ depending on tumor type and progression. We have reported, using animal models, that local chymase injection strongly facilitates angiogenesis [3]. Recently, we documented that there was a strong correlation between the number of vessels and the concentration of chymase-positive cells around stomach cancers and that the postoperative survival rate for patients with high chymase-positive cell concentrations was lower when compared to patients with low chymase-positive cell concentrations [4]. These results strongly suggest the possibility that chymase facilitates angiogenesis, thus subsequently advancing cancer growth.

The functions of mast cells around cancers cannot be ascertained based solely on our results. However, based at least on our past studies, chymase-positive cells are involved in cancer angiogenesis. Yet, as stated by Ozdemir, mast cells contain many substances that facilitate angiogenesis and substances that are toxic to cancer cells. Hence, the roles of mast cells may differ depending on cancer differentiation and progression. Not all mast cells contain chymase, and its expression is seen in only about half the cells. Therefore, we would like to strongly emphasize that whether or not mast cells contain chymase is a very important point. However, clarifying the role of chymase-positive mast cells in angiogenesis and cancer growth will require clinical study using a chymase inhibitor.

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;28:617.[Abstract/Free Full Text]
  2. Ozdemir O, Ravindranath Y, Savasan S. Short term mast cell natural cell-mediated cytotoxicity. Ann Allergy Asthma Immunol 2004;94:186[abstract].
  3. Muramatsu M, Katada J, Hayashi I, Majima M. Chymase as a proangiogenic factor. A possible involvement of chymase-angiotensin-dependent pathway in the hamster sponge angiogenesis model. J Biol Chem 2000;275:5545.[Abstract/Free Full Text]
  4. Kondo K, Muramatsu M, Okamoto Y, Jin D, Takai S, Tanigawa N, Miyazaki M. Expression of chymase-positive cells in gastric cancer and its correlation with the angiogenesis. J Surg Oncol 2006;93:36.[Medline]




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