Abstract 1102: Neutrophils impact on growth and mobility of human colorectal cancer cells

Abstract

Abstract Colorectal cancer (CRC) represents the third most common cancer worldwide, with higher prevalence in developed regions. In Switzerland, about 6000 patients are diagnosed with CRC each year with a mortality rate of approximately 1600 deaths in both sexes, largely exceeding European yearly rates. In clinical practice, administration of monoclonal antibodies (mAb) against Epithelial Growth Factor Receptor (EGFR), alone or in combination with chemotherapy, represents a potential treatment. MAbs have the capacity to induce antibody-dependent cell mediated cytotoxicity through CD16 crosslinking on NK cells. However, NK cells poorly infiltrate human CRC tissues and they are devoid of prognostic value. In contrast, CRC-infiltration by granulocytes has been shown to represent an independent prognostic factor. Since granulocytes are CD16 (FcgRIII)+, the capacity of anti-EGFR immunotherapies to modulate neutrophils functions might crucially influence their clinical outcome. Here we explored direct effects of granulocytes on CRC cell proliferation and mobility “in vitro”. The scope of this study is to investigate directs effect of neutrophils (N) on CRC cell growth in the presence or absence of anti-EGFR mAb. First we investigated the effect of N, per se, on CRC cell growth in vitro. We observed that N did not inhibit the proliferation of DLD-1 cells, as assessed by 3HTdR incorporation. However, DLD-1 cells conditioned by human N showed a reduced adhesion on impedance-based cell sensing surfaces. These contrasting results may suggest that in the presence of N, DLD-1 cells could acquire the capacity to proliferate in a contact-independent manner. As a consequence, N-conditioned CRC could become more mobile. Indeed, we observed that DLD-1 cells exhibited an increased migratory capacity after co-culture with N, whereas their capacity to invade matrigel-coated surfaces was not affected. We are currently assessing the migration of CRC conditioned by resting and activated N towards molecularly defined metabolites (i. e. Glucose, Butyrrate), as well as, the expression of genes and proteins involved in cell migration. Whether EGFR antagonists can impact on tumor cell migration is currently unknown. We therefore plan to study whether anti-EGFR mAbs, which can effectively block the growth of DLD-1 and A431 cells in co-cultured with CD16+ lymphocytes, can also block N-induced CRC migration. Our data document that N fail to inhibit CRC cell proliferation “in vitro” and increase their mobility. In vivo anti-tumor effects might be related to other components of the tumor microenvironment. Citation Format: Valeria Governa, Luca Quagliata, Valentina Mele, Christian Hirt, Luigi Terracciano, Giulio C. Spagnoli, Elisabetta Padovan. Neutrophils impact on growth and mobility of human colorectal cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1102. doi:10.1158/1538-7445.AM2014-1102