Selection with melphalan or paclitaxel (Taxol) yields variants with different patterns of multidrug resistance, integrin expression and in vitro invasiveness

被引:60
作者
Liang, Y
Meleady, P
Cleary, I
McDonnell, S
Connolly, L
Clynes, M [1 ]
机构
[1] Dublin City Univ, Natl Inst Cellular Biotechnol, Natl Cell & Tissue Culture Ctr, Dublin 9, Ireland
[2] Dublin City Univ, Sch Biotechnol, Dublin 9, Ireland
关键词
melphalan; paclitaxel (taxol); multidrug resistance (MDR); invasion; multidrug resistance protein (MRP); integrin; matrix metalloproteinase (MMP);
D O I
10.1016/S0959-8049(01)00086-7
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
A melphalan-resistant variant (Roswell Park Memorial Institute (RPMI)-2650M1) and a paclitaxel-resistant variant (RPMI-1650Tx) of the drug-sensitive human nasal carcinoma cell line, RPMI-2650. were established. The multidrug resistance (MDR) phenotype in the RPMI-2650Tx appeared to be P-glycoprotein (PgP)-mediated. Overexpression of multidrug resistant protein (MRP) family members was observed in the RPMI-2650M1 cells, which were also much more invasive in vitro than the parental cell line or the paclitaxel-resistant variant. Increased expression of alpha (2), alpha (5), alpha (6), beta (1) and beta (4) integrin subunits, decreased expression of alpha (4) integrin subunit, stronger adhesion to collagen type IV, laminin, fibronectin and matrigel, increased expression of MMP-2 and MMP-9 and significant motility compared with the parental cells were observed, along with a high invasiveness in the RPMI-7650M1 cells. Decreased expression of the alpha (2) integrin subunit, decreased attachment to collagen type IV, absence of cytokeratin 18 expression, no detectable expression of gelatin-degrading proteases and poor motility may be associated with the non-invasiveness of the RPMI-2650Tx variant. These results suggest that melphalan exposure can result in not only a MDR phenotype. but could also make cancer cells more invasive, whereas paclitaxel exposure resulted in MDR without increasing the in vitro invasiveness in the RPMI-2650 cells. (C) 2001 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:1041 / 1052
页数:12
相关论文
共 47 条
[1]  
ALBINI A, 1987, CANCER RES, V47, P3239
[2]   CHEMOSENSITISATION AND DRUG ACCUMULATION EFFECTS OF CYCLOSPORINE-A, PSC-833 AND VERAPAMIL IN HUMAN MDR LARGE CELL LUNG-CANCER CELLS EXPRESSING A 190K MEMBRANE-PROTEIN DISTINCT FROM P-GLYCOPROTEIN [J].
BARRAND, MA ;
RHODES, T ;
CENTER, MS ;
TWENTYMAN, PR .
EUROPEAN JOURNAL OF CANCER, 1993, 29A (03) :408-415
[3]   CLONES OF TUMOR-CELLS DERIVED FROM A SINGLE PRIMARY HUMAN LUNG-TUMOR REVEAL DIFFERENT PATTERNS OF BETA(1)-INTEGRIN EXPRESSION [J].
CHEN, FA ;
ALOSCO, T ;
CROY, BA ;
NARUMI, K ;
PERCY, DH ;
BANKERT, RB .
CELL ADHESION AND COMMUNICATION, 1994, 2 (04) :345-357
[4]   Single treatment with cisplatin or UFT, but not their combination treatment enhances the metastatic capacity of mouse fibrosarcoma cells [J].
Choi, S ;
Okada, F ;
Kobayashi, M ;
Habelhah, H ;
Nakae, D ;
Konishi, Y ;
Totsuka, Y ;
Hosokawa, M .
ANTI-CANCER DRUGS, 1999, 10 (02) :235-243
[5]  
CILLO C, 1987, CANCER RES, V47, P2604
[6]   DRUG-RESISTANCE IN KHT FIBRO-SARCOMA CELL-LINES WITH DIFFERENT METASTATIC ABILITY [J].
CILLO, C ;
LING, V ;
HILL, RP .
INTERNATIONAL JOURNAL OF CANCER, 1989, 43 (01) :107-111
[7]  
Cleary I, 1997, BIOCHEM PHARMACOL, V53, P1493
[8]   MULTIPLE DRUG-RESISTANCE IN VARIANT OF A HUMAN NONSMALL CELL LUNG-CARCINOMA CELL-LINE, DLKP-A [J].
CLYNES, M ;
REDMOND, A ;
MORAN, E ;
GILVARRY, U .
CYTOTECHNOLOGY, 1992, 10 (01) :75-89
[9]  
Clynes M, 1998, MULTIPLE DRUG RESIST
[10]   Cell adhesion mediated drug resistance (CAM-DR): Role of integrins and resistance to apoptosis in human myeloma cell lines [J].
Damiano, JS ;
Cress, AE ;
Hazlehurst, LA ;
Shtil, AA ;
Dalton, WS .
BLOOD, 1999, 93 (05) :1658-1667