PMID- 10048981
OWN - NLM
STAT- MEDLINE
DCOM- 19990225
LR  - 20190708
IS  - 0020-7136 (Print)
IS  - 0020-7136 (Linking)
VI  - 80
IP  - 5
DP  - 1999 Mar 1
TI  - Monocyte chemoattractant protein-1 gene modification of multidrug-resistant human 
      lung cancer enhances antimetastatic effect of therapy with anti-P-glycoprotein 
      antibody in SCID mice.
PG  - 773-80
AB  - Distant metastases and multidrug resistance are critical problems in the therapy 
      of human small cell lung cancer (SCLC). In this study, we investigated whether 
      transduction of the monocyte chemoattractant protein-1 (MCP-1) gene into 
      multidrug-resistant (MDR) human lung cancer cells affected the formation of 
      metastases or their inhibition by the anti-P-glycoprotein (P-gp) monoclonal 
      antibody (MAb) MRK16. MDR human SCLC (H69/VP) cells were transduced with the 
      human MCP-1 gene inserted into the expression vector BCMGSNeo. MCP-1 gene 
      transduction had no effect on drug sensitivity, the expression of surface 
      antigens or the in vitro proliferation of H69/VP cells. Using the metastatic 
      model of NK cell-depleted SCID mice, H69/VP cells transduced with the MCP-1 gene 
      were inoculated intravenously (i.v.) and formed metastatic colonies in the liver, 
      kidneys and lymph nodes, similar to those formed by parent or mock-transduced 
      cells. However, systemic treatment of the mice with MRK16 reduced the metastases 
      of H69/VP cells in the liver, kidneys and lymph nodes, and was significantly more 
      effective in inhibiting the metastases of MCP-1 producing H69/VP than those of 
      mock-transduced cells. MCP-1 gene transduction significantly prolonged the 
      survival of tumor-bearing mice treated with MRK16. Our findings suggest that 
      local production of MCP-1 in the tumor site increases the anti-P-gp 
      antibody-dependent cell-mediated cytotoxicity, and the MCP-1 gene-induced 
      modification of MDR human SCLC cells thereby enhances the antimetastatic effect 
      of therapy with anti-P-gp antibody. Thus, the accumulation of effector cells in 
      the tumor site is a very important factor in the therapy using the anti-P-gp 
      antibody.
FAU - Nokihara, H
AU  - Nokihara H
AD  - Third Department of Internal Medicine, University of Tokushima School of 
      Medicine, Japan.
FAU - Nishioka, Y
AU  - Nishioka Y
FAU - Yano, S
AU  - Yano S
FAU - Mukaida, N
AU  - Mukaida N
FAU - Matsushima, K
AU  - Matsushima K
FAU - Tsuruo, T
AU  - Tsuruo T
FAU - Sone, S
AU  - Sone S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 1)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Recombinant Proteins)
RN  - 6PLQ3CP4P3 (Etoposide)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 1/*immunology
MH  - Animals
MH  - Antibodies, Monoclonal/*therapeutic use
MH  - Carcinoma, Small Cell/*genetics/*therapy
MH  - Chemokine CCL2/biosynthesis/*genetics
MH  - Clone Cells
MH  - *Drug Resistance, Multiple
MH  - Etoposide/toxicity
MH  - Humans
MH  - Immunotherapy
MH  - Lung Neoplasms/*genetics/pathology/*therapy
MH  - Mice
MH  - Mice, SCID
MH  - Neoplasm Metastasis/prevention & control
MH  - Organ Specificity
MH  - Recombinant Proteins/biosynthesis
MH  - Transfection
MH  - Tumor Cells, Cultured
EDAT- 1999/02/27 03:15
MHDA- 2000/06/20 09:00
CRDT- 1999/02/27 03:15
PHST- 1999/02/27 03:15 [pubmed]
PHST- 2000/06/20 09:00 [medline]
PHST- 1999/02/27 03:15 [entrez]
AID - 10.1002/(SICI)1097-0215(19990301)80:5<773::AID-IJC23>3.0.CO;2-E [pii]
AID - 10.1002/(sici)1097-0215(19990301)80:5<773::aid-ijc23>3.0.co;2-e [doi]
PST - ppublish
SO  - Int J Cancer. 1999 Mar 1;80(5):773-80. doi: 
      10.1002/(sici)1097-0215(19990301)80:5<773::aid-ijc23>3.0.co;2-e.