PMID- 10357555
OWN - NLM
STAT- MEDLINE
DCOM- 19990615
LR  - 20190831
IS  - 0344-5704 (Print)
IS  - 0344-5704 (Linking)
VI  - 43 Suppl
DP  - 1999
TI  - Heterogeneity of multiorgan metastases of human lung cancer cells genetically 
      engineered to produce cytokines and reversal using chimeric monoclonal antibodies 
      in natural killer cell-depleted severe combined immunodeficient mice.
PG  - S26-31
AB  - Lung cancer is a major cause of cancer deaths, most of which can be attributed to 
      distant multiorgan metastases. To examine the cellular and molecular mechanisms 
      of lung cancer metastasis to distant organs, we have established novel models of 
      human lung cancer (small cell and non-small cell lung cancer) metastasis in 
      natural killer cell-depleted severe combined immunodeficient (SCID) mice. We 
      investigated whether local production of the cytokines responsible for regulation 
      of macrophage function at tumor growth sites affects the pattern of lung cancer 
      metastasis in distant organs. Several lung cancer cell lines were genetically 
      engineered to produce human macrophage colony-stimulating factor (M-CSF) and 
      monocyte chemoattractant protein-1 (MCP-1), and their metastatic potentials were 
      assessed. Interestingly, M-CSF gene transduction had an antimetastatic effect for 
      the liver and lymph nodes, but not the kidneys. In contrast, MCP-1 gene-modified 
      lung cancer cells and their parent cells had identical metastatic potentials. 
      These findings indicate a possible role for cytokines and suggest that lung 
      cancer has metastatic heterogeneity. Examining ways of controlling human lung 
      cancer metastases, we investigated the antimetastatic effect of chimeric 
      monoclonal antibodies (MAbs) against P-glycoprotein and ganglioside GM2 (MH162 
      and KM966, respectively). Both MAbs, when given on days 2 and 7, inhibited the 
      development of distant metastases of lung cancer in a dose-dependent fashion. 
      Combined use of anti-P-glycoprotein MAb with M-CSF or MCP-1 gene transduction 
      caused complete inhibition of metastasis of H69/VP cells. The antimetastatic 
      effect of these MAbs in vivo was mainly due to an antibody-dependent 
      cell-mediated cytotoxicity reaction mediated by mouse macrophages. These findings 
      suggest that the mouse-human chimeric MAb in combination with cytokine gene 
      transduction may be useful for the eradication of lung cancer metastases in 
      humans.
FAU - Sone, S
AU  - Sone S
AD  - Third Department of Internal Medicine, University of Tokushima School of 
      Medicine, Japan.
FAU - Yano, S
AU  - Yano S
FAU - Hanibuchi, M
AU  - Hanibuchi M
FAU - Nokihara, H
AU  - Nokihara H
FAU - Nishimura, N
AU  - Nishimura N
FAU - Miki, T
AU  - Miki T
FAU - Nishioka, Y
AU  - Nishioka Y
FAU - Shinohara, T
AU  - Shinohara T
LA  - eng
PT  - Journal Article
PL  - Germany
TA  - Cancer Chemother Pharmacol
JT  - Cancer chemotherapy and pharmacology
JID - 7806519
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 1)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 19600-01-2 (G(M2) Ganglioside)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 1/immunology
MH  - Animals
MH  - Antibodies, Monoclonal/*pharmacology
MH  - Carcinoma, Non-Small-Cell Lung/immunology/*pathology/secondary/therapy
MH  - Carcinoma, Small Cell/immunology/*pathology/secondary/therapy
MH  - Chemokine CCL2/metabolism
MH  - Cytokines/*biosynthesis
MH  - G(M2) Ganglioside/immunology
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/metabolism
MH  - Humans
MH  - Kidney Neoplasms/*pathology/secondary/therapy
MH  - Killer Cells, Natural/*immunology
MH  - Liver Neoplasms/immunology/*pathology/secondary/therapy
MH  - Lung Neoplasms/genetics/immunology/metabolism/*pathology
MH  - Lymphatic Metastasis
MH  - Mice
MH  - Mice, SCID
MH  - Neoplasm Transplantation
MH  - Recombinant Fusion Proteins/*pharmacology
MH  - Transduction, Genetic
MH  - Tumor Cells, Cultured
EDAT- 1999/06/05 00:00
MHDA- 1999/06/05 00:01
CRDT- 1999/06/05 00:00
PHST- 1999/06/05 00:00 [pubmed]
PHST- 1999/06/05 00:01 [medline]
PHST- 1999/06/05 00:00 [entrez]
AID - 10.1007/s002800051094 [doi]
PST - ppublish
SO  - Cancer Chemother Pharmacol. 1999;43 Suppl:S26-31. doi: 10.1007/s002800051094.