Abstract 3130: Zoledronic acid inhibits proliferation and metastasis of human pancreatic cancer in the patient-derived orthotopic xenograft (PDOX) model by targeting tumor-educated macrophages

• Published in: Cancer research (Chicago, Ill.) Ill.), 2014-10, Vol.74 (19_Supplement), p.3130-3130
• Main Authors: Hiroshima, Yukihiko, Hassenein, Mohamed K., Menen, Rhiana, Katz, Matthew H.g., Fleming, Jason B., Sato, Sho, Murakami, Takashi, Yamamoto, Mako, Uehara, Fuminari, Miwa, Shinji, Yano, Shuya, Momiyama, Masashi, Maawy, Ali, Chishima, Takashi, Tanaka, Kuniya, Bouvet, Michael, Endo, Itaru, Hoffman, Robert M.
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2014-3130

Macrophages harvested from the peritoneal cavity of nude mice with subcutaneous human pancreatic tumors were defined as “tumor-educated macrophages” (EMϕ) and macrophages harvested from mice without tumors were defined as “naïve macrophages” (NMϕ). EMϕ promote tumor growth and metastasis. The aim of the present study was to determine the efficacy of Zoledronic acid (ZA) on EMϕ in a pancreatic cancer patient derived orthotopic xenograft (PDOX) nude mouse model. In this study, EMϕ and NMϕ were compared for their ability to enhance tumor progression. We initially demonstrated that the cancer cells exposed to the conditioned medium harvested from EMϕ culture significantly increased proliferation (p = 0.016) and had more migration stimulation capability (p < 0.001) compared to cultured cancer cells treated with the conditioned medium from NMϕ. Next, we examined the efficacy of ZA on EMϕ, and NMϕ and found that ZA had the ability to kill both EMϕ and NMϕ in vitro. We then demonstrated that EMϕ promoted tumor growth and metastasis in an orthotopic mouse model of a human pancreatic cancer cell line, ZA reduced the tumor growth (p = 0.006) and metastasis (p = 0.025) promoted by EMϕ. Finally, we examined the efficacy of ZA for pancreatic cancer in the PDOX model, and found that the combination of gemcitabine (GEM) and ZA reduced tumor weight (p = 0.016) and tumor growth (p = 0.005) compared to GEM alone. ZA alone reduced metastasis (p = 0.009). These results suggest that ZA inhibits the proliferation and the metastasis of human pancreatic cancer by targeting EMϕ. Citation Format: Yukihiko Hiroshima, Mohamed K. Hassenein, Rhiana Menen, Matthew H.g. Katz, Jason B. Fleming, Sho Sato, Takashi Murakami, Mako Yamamoto, Fuminari Uehara, Shinji Miwa, Shuya Yano, Masashi Momiyama, Ali Maawy, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Itaru Endo, Robert M. Hoffman. Zoledronic acid inhibits proliferation and metastasis of human pancreatic cancer in the patient-derived orthotopic xenograft (PDOX) model by targeting tumor-educated macrophages. [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 3130. doi:10.1158/1538-7445.AM2014-3130