May Mast Cells Have Any Effect in New Modalities of Cancer Treatment?

Multifunctional mast cells (MC) have been recently reported as effectors in the human innate and even adaptive immune system, besides their known roles in allergic disorders. First in vivo observations in the 1950`s suggested their possible role as anti-tumor cells around certain solid tumors and questioned their interactions with tumor cells (Prior, 1953). Later, in vitro murine mast cell cytotoxicity (MCC) against murine tumor cells was described in 1981 (Henderson, 1981; Ghiara, 1985; Richards 1988). However, to the best of our knowledge, there is no reported data on in vitro human MCC against human tumor cells. Current in vivo observations and implications from human pathological specimens are also very controversial. Moreover, there is still difficulty in obtaining and maintaining human MCs in cultures since they have low expansion potential. These facts have hampered in vitro human MC studies up to the last decades of the 20th century. The recent use of methylcellulose media for in vitro human MC cultures increased the knowledge and data strongly supporting an increasing role of MC as effector elements of innate immunity (Leskinen, 2003; Marshall, 2004; Della Rovere, 2009; Özdemir, 2007, 2011). Ambiguous and mounting evidence also indicates that MCs accumulate around tumors and could either promote or inhibit tumor growth, most likely depending on environmental conditions. Presently, believers in the inhibitory role of MCs assume them to be inhibitors of tumor development through their cytotoxic pro-necrolytic/-apoptotic granules (WagelieSteffen, 1998; Leskinen, 2003; Kataoka, 2004; Pardo, 2007; Heikkilä, 2008). In fact, the MC has been long believed to have natural cytotoxicity against murine TNF-α sensitive tumor cells in the long term incubations (>24h), by either TNF-α dependent or independent pathways. TNF-α independent pathways like cathepsin G, NO, serine proteases, peroxidases, H2O2 etc. were also assumed to contribute to MCC (Henderson, 1981; Ghiara, 1985; Richards 1988). Moreover, in vitro murine MCC has been well demonstrated against TNF-α-sensitive murine WEHI-164 and L929 tumor cells. Murine MCC seems to be different from natural killer (NK) cytotoxicity by means of acting in long term against unusual targets such as WEHI-164 and L929 with different mediators like peroxidases (Henderson, 1981; Ghiara, 1985; Richards 1988). Moreover, the last decade of research demonstrates that MC granules have pro-apoptotic characteristics (Wagelie-Steffen, 1998; Leskinen, 2003; Kataoka, 2004; Pardo, 2007; Heikkilä, 2008). Chymase was shown to induce apoptosis, and apoptotic