Abstract 316: Peritoneal carcinomatosis depends for growth and spreading on endogenous inflammatory cues generated by infiltrating macrophages

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Abstract Peritoneal carcinomatosis is the most common terminal feature of abdominal cancers. Interfering with the peritoneal immune microenvironment is a promising tool for combinational therapy. Preclinical studies on peritoneal carcinomatosis have been hampered by the limited availability of models as well as non-invasive methods to follow tumor growth. We set up ad hoc models via the orthotopic injection of murine cells lines in immuno-competent mice and followed tumor growth by imaging with [18F]2-fluoro-2-deoxy-D-glucose-PET ([18F]-FDG-PET). Colon carcinoma (MC38), Mouse Ovarian Surface Epithelial Carcinoma cell line (MOSEC) of C57BL/6 origin and adenocarcinoma cells (TS/A) of Balb/C origin were injected intraperitoneally in syngeneic mice. The models nicely recapitulated the histological features of the human disease: carcinoma cells distributed along the cavity and yielded several masses attached to the peritoneal lining. Animals were longitudinally followed by imaging with [18F]-FDG-PET: tumor lesions selectively up-took the radioactive tracer and we observed a significant correlation between lesion dimension and metabolic radioactive volume. We characterized leukocyte composition of the peritoneal liquid of tumor bearing mice by multicolor flow cytometry, performing peritoneal lavage on live animals at various time points during tumor growth. Tumor spreading induced the recruitment of leukocytes, among which the most relevant population was represented by CD45+CD11b+F4/80+ monocytes/macrophages. The depletion of peritoneal monocytes/macrophages, via administration of clodronate encapsulated in liposomes, lead to a substantial reduction of tumor burden as well as leukocyte recruitment, and was paralleled by a decrement in the extent of radioactivity distribution when imaging mice with [18F]-FDG-PET. Moreover we found out that colon carcinoma cells upon in-vitro treatment with stress-inducing stimuli, such as starvation and chemotherapeutic agents exposure, produced factors involved in leukocytes recruitment: this behavior was directly linked to the activation of autophagic and apoptotic intracellular pathways. In conclusion, [18F]-FDG-PET imaging allowed the non-invasive detection of peritoneal adenocarcinoma lesions which spreading and growth was dependent on the production of factors involved in leukocytes recruitment, specifically on peritoneal monocytes/macrophages. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 316. doi:1538-7445.AM2012-316

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