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BioMed Research International
Volume 2014 (2014), Article ID 241571, 13 pages
http://dx.doi.org/10.1155/2014/241571
Research Article

Adhesion of Pancreatic Cancer Cells in a Liver-Microvasculature Mimicking Coculture Correlates with Their Propensity to Form Liver-Specific Metastasis In Vivo

1Institute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan
2LIMMS/CNRS UMI2820 Institute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan
3Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan
4The Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan

Received 8 December 2013; Revised 10 April 2014; Accepted 12 April 2014; Published 11 May 2014

Academic Editor: Qing He

Copyright © 2014 Mohammad Mahfuz Chowdhury et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Organ-specific characteristic of endothelial cells (ECs) is crucial for specific adhesion of cancer cells to ECs, which is a key factor in the formation of organ-specific metastasis. In this study, we developed a coculture of TMNK-1 (immortalized liver sinusoidal ECs) with 10T1/2 (resembling hepatic stellate cells) to augment organ-specific characteristic of TMNK-1 and investigated adhesion of two pancreatic cancer cells (MIA-PaCa-2 and BxPC-3) in the culture. MIA-PaCa-2 and BxPC-3 adhesion in TMNK-1+10T1/ coating culture (TMNK-1 monolayer over 10T1/2 layer on collagen coated surface) were similar. However, in TMNK-1+10T1/ gel (coculture on collagen gel surface), MIA-PaCa-2 adhesion was significantly higher than BxPC-3, which was congruent with the reported higher propensity of MIA-PaCa-2 than BxPC-3 to form liver metastasis in vivo. Notably, as compared to BxPC-3, MIA-PaCa-2 adhesion was lower and similar in TMNK-1 only culture on the collagen coated and gel surfaces, respectively. Investigation of the adhesion in the representative human umbilical vein ECs (HUVECs) cultures and upon blocking of surface molecules of ECs revealed that MIA-PaCa-2 adhesion was strongly dependent on the organ-specific upregulated characteristics of TMNK-1 in TMNK-1+10T1/ gel culture. Therefore, the developed coculture would be a potential assay for screening novel drugs to inhibit the liver-microvasculature specific adhesion of cancer cells.