Interaction between CD44 and hyaluronate induces chemoresistance in non-small cell lung cancer cell.
CD44s is a principle hyaluronate (HA) receptor and has been reported to play an important role in cancer cell invasion and metastasis. The aim of our study is to determine if the interaction between HA and CD44s influences in vitro chemosensitivity of non-small cell lung cancer (NSCLC). NSCLC cell line, H322 cells, transfected with the CD44s gene (H322/CD44s) cultured on HA coated plates were more resistant to cisplatin (CDDP) than that on bovine serum albumin. Multidrug resistance protein2 (MRP2) expression was induced in H322/CD44s cells cultured on HA. MRP2 inhibitor, MK571, not only suppressed MRP2 expression but also reversed CDDP resistance. These results suggest that the interaction between CD44s and HA play a pivotal role in acquired resistance to CDDP in NSCLC and MRP2 could be involved in this potential mechanism.
Ohashi
Rina
R
Department of Respiratory Medicine, Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan. rinaohas@med.juntendo.ac.jp
Takahashi
Fumiyuki
F
Cui
Ri
R
Yoshioka
Masakata
M
Gu
Tao
T
Sasaki
Shinichi
S
Tominaga
Shigeru
S
Nishio
Kazuto
K
Tanabe
Kenneth K
KK
Takahashi
Kazuhisa
K
D017209:Apoptosis; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple; D005455:Fluorescent Antibody Technique; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000378:metabolism*; D020287:In Situ Nick-End Labeling; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D026901:Membrane Transport Proteins / Q000378:metabolism; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism
D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid; D026901:Membrane Transport Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C000715087:ABCC2 protein, human