Oncotarget

Research Papers:

Splenectomy is associated with an aggressive tumor growth pattern and altered host immunity in an orthotopic syngeneic murine pancreatic cancer model

Ho Kyoung Hwang, Takashi Murakami, Tasuku Kiyuna, Se Hoon Kim, Sung Hwan Lee, Chang Moo Kang, Robert M. Hoffman and Michael Bouvet _

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Oncotarget. 2017; 8:88827-88834. https://doi.org/10.18632/oncotarget.21331

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Abstract

Ho Kyoung Hwang1,2,3, Takashi Murakami1,2,4, Tasuku Kiyuna1,2,5, Se Hoon Kim6, Sung Hwan Lee3, Chang Moo Kang3, Robert M. Hoffman1,2 and Michael Bouvet1

1Department of Surgery, University of California, San Diego, CA, USA

2AntiCancer, Inc., San Diego, CA, USA

3Department of Surgery, Division of Hepatobiliary and Pancreas Surgery, Severance Hospital, The Graduate School, Yonsei University College of Medicine, Seoul, Korea

4Graduate School of Medicine, Yokohama City University, Yokohama, Japan

5Department of Orthopedic Surgery, University of the Ryukyus, Okinawa, Japan

6Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea

Correspondence to:

Michael Bouvet, email: mbouvet@ucsd.edu

Keywords: pancreatic cancer, orthotopic mouse models, splenectomy, tumor infiltrating lymphocytes, metastases

Received: July 31, 2017    Accepted: August 21, 2017    Published: September 28, 2017

ABSTRACT

The purpose of this study was to investigate whether splenectomy influences the tumor growth and metastatic pattern in an orthotopic syngeneic murine pancreatic cancer model. Murine pancreatic cancer cells (PAN02) were subcutaneously injected into the flanks of nude mice. A small tumor fragment (3 mm2), harvested from a subcutaneous tumor. was orthotopically implanted in the tail of the pancreas of C57/BL6 mice without splenectomy (control group, n=15) or with simultaneous splenectomy (splenectomy group, n=15). Tumor growth and metastatic patterns were analyzed by laparotomy at 21 days after surgery. No tumor growth was found in 5 mice (33.3%) of the control group and 1 mouse (6.7%) of the splenectomy group (p=0.169). Tumor volume was significantly larger in splenectomy group (p=0.013). Peritoneal seeding was more frequently observed in the splenectomy group (11 (73.3%) vs. 4 (26.7%), p=0.011). There were no differences in the number of liver and kidney metastasis between the two groups. The ratios of tumor-infiltrating CD4+ to FoxP3+ and CD8+ to FoxP3+ were significantly higher in the control group compared to the splenectomy group (8.2 ± 9.3 vs. 2.4 ± 1.5, p=0.046; 2.5 ± 1.4 vs. 1.5 ± 0.4, p=0.031, respectively). Splenectomy enhanced tumor growth and peritoneal seeding in an orthotopic syngeneic murine pancreatic cancer mouse model. The ramification of these results are discussed for pancreatic cancer treatment.


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