Suppression of SERPINA1-albumin complex formation by galectin-3 overexpression leads to paracrine growth promotion of chronic myelogenous leukemia cells

Ryuko Nakayama; Junya Kuroda; Nobuko Taniyama; Mio Yamamoto-Sugitani; Sayori Wada; Miki Kiyota; Shinsuke Mizutani; Yoshiaki Chinen; Yosuke Matsumoto; Hisao Nagoshi; Yuji Shimura; Tsutomu Kobayashi; Shigeo Horiike; Kenji Sato; Masafumi Taniwaki

doi:10.1016/j.leukres.2013.07.026

Suppression of SERPINA1-albumin complex formation by galectin-3 overexpression leads to paracrine growth promotion of chronic myelogenous leukemia cells

Leuk Res. 2014 Jan;38(1):103-8. doi: 10.1016/j.leukres.2013.07.026. Epub 2013 Aug 13.

Authors

Affiliations

¹ Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
² Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan. Electronic address: junkuro@koto.kpu-m.ac.jp.
³ Division of Applied Life Sciences, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Kyoto, Japan.

PMID: 23953881
DOI: 10.1016/j.leukres.2013.07.026

Abstract

Galectin-3 is induced in chronic myelogenous leukemia (CML) cells by co-culture with bone marrow stromal cells, making paracrine growth promotion of CML cells in conditioned medium (CM) from galectin-3 overexpressing CML cells more potent. We used gel filtration chromatography to demonstrate that the bovine SERPINA1-fetal bovine serum albumin (BSA) complex was specifically suppressed in CM from galectin-3 overexpressing cells. The SERPINA1-BSA complex as well as human plasma SERPINA1 inhibited the growth of CML cells, while exogenous galectin-3 partly offset this effect. These findings suggest that galectin-3 overexpression promotes paracrine growth of CML cells by interfering with the action of the growth inhibitory SERPINA1-albumin complex.

Keywords: Bone marrow stromal cell; Chronic myelogenous leukemia; Galectin-3; SERPINA1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis / drug effects
Bone Marrow Cells / drug effects
Bone Marrow Cells / metabolism
Cattle
Cell Line
Cell Line, Tumor
Cell Proliferation*
Coculture Techniques
Culture Media, Conditioned / pharmacology
Cytokines / metabolism
Dose-Response Relationship, Drug
Electrophoresis, Polyacrylamide Gel
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Galectin 3 / genetics
Galectin 3 / metabolism*
Humans
K562 Cells
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
Serum Albumin / chemistry
Serum Albumin / metabolism*
Serum Albumin / pharmacology
Serum Albumin, Bovine / chemistry
Serum Albumin, Bovine / metabolism
Serum Albumin, Bovine / pharmacology
Tumor Microenvironment / drug effects
alpha 1-Antitrypsin / chemistry
alpha 1-Antitrypsin / metabolism*
alpha 1-Antitrypsin / pharmacology

Substances

Culture Media, Conditioned
Cytokines
Galectin 3
SERPINA1 protein, human
Serum Albumin
alpha 1-Antitrypsin
Serum Albumin, Bovine