Abstract A68: Utilizing fibroblast recruitment for detection of ovarian microtumors in the abdomen

Abstract

Abstract Ovarian cancer is the most lethal gynecologic malignancy among women in the United States and other industrial nations [1]. Metastatic involvement of the peritoneal cavity is abundant in 70% of the patients[2]. Tumor cells settle on the omentum layer and other surfaces in the cavity and are massively present in ascetic fluid. Ovarian tumors are characterized by relatively high contribution of stroma cells (fibroblasts, immune cells, endothelial cells and others) [3]. The progression of ovarian carcinoma from transformation stage through tumor formation and metastasis relies on the complex interaction between cancer and stroma cells and microenvironment (reviewed in [4]). Cancer associated fibroblasts (CAF) are a dominant component of the tumor stroma and are involved in the clinical outcome of the tumor and metastatic process. Fibroblasts have a dual role in tumor progression; Normal fibroblasts inhibit preneoplastic growth in normal tissues, but in response to tumor stimuli, activated fibroblasts can promote invasion and migration of cancer cells [4, 5]. We have previously demonstrated specific and massive homing of labeled fibroblasts to ovarian tumors [6]. In this work we wish to demonstrate the use possibility to use naïve fibroblasts for detection of ovarian metastasis model. CD1-nu mice were injected intra-peritoneally with fluorescently labeled ovarian cancer ES2 cells/spheroids. A week later fluorescently labeled CV1 fibroblasts were injected intra-peritoneally. Our results show specific homing of the fibroblasts to the tumor cell location. The fibroblasts highlighted all the tumor nodules with very low residual false positive labeling. Thus we achieve high selectivity and specificity for detection of tumors including very small non-angiogenic clusters of tumor cells. Surgery compatible fluorescence imaging systems are now commercially available. However, the lack of fluorescent probes with sufficient specificity and selectivity limits the application of these tools for surgical guidance. If homing of fibroblasts to tumors proves to be as specific and sensitive as suggested from the preclinical data, it could be used for intra-operative guidance of biopsy so as to improve accuracy of critical clinical decisions; as well as for image guided surgical debulking. 1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ: Cancer statistics, 2009. CA Cancer J Clin 2009, 59:225-249. 2. Lengyel E: Ovarian cancer development and metastasis. Am J Pathol, 177:1053-1064. 3. Labiche A, Heutte N, Herlin P, Chasle J, Gauduchon P, Elie N: Stromal compartment as a survival prognostic factor in advanced ovarian carcinoma. Int J Gynecol Cancer, 20:28-33. 4. Schauer IG, Sood AK, Mok S, Liu J: Cancer-associated fibroblasts and their putative role in potentiating the initiation and development of epithelial ovarian cancer. Neoplasia, 13:393-405. 5. Nagy JA, Brown LF, Senger DR, Lanir N, Van de Water L, Dvorak AM, Dvorak HF: Pathogenesis of tumor stroma generation: a critical role for leaky blood vessels and fibrin deposition. Biochim Biophys Acta 1989, 948:305-326. 6. Granot D, Addadi Y, Kalchenko V, Harmelin A, Kunz-Schughart LA, Neeman M: In vivo imaging of the systemic recruitment of fibroblasts to the angiogenic rim of ovarian carcinoma tumors. Cancer Res 2007, 67:9180-9189. Citation Format: Roni Oren, Michal Neeman. Utilizing fibroblast recruitment for detection of ovarian microtumors in the abdomen. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr A68.