PMID- 11359798
OWN - NLM
STAT- MEDLINE
DCOM- 20010816
LR  - 20220321
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 166
IP  - 11
DP  - 2001 Jun 1
TI  - Low-level monocyte chemoattractant protein-1 stimulation of monocytes leads to 
      tumor formation in nontumorigenic melanoma cells.
PG  - 6483-90
AB  - Tumors commonly produce chemokines for recruitment of host cells, but the 
      biological significance of tumor-infiltrating inflammatory cells, such as 
      monocytes/macrophages, for disease outcome is not clear. Here, we show that all 
      of 30 melanoma cell lines secreted monocyte chemoattractant protein-1 (MCP-1), 
      whereas normal melanocytes did not. When low MCP-1-producing melanoma cells from 
      a biologically early, nontumorigenic stage were transduced to overexpress the 
      MCP-1 gene, tumor formation depended on the level of chemokine secretion and 
      monocyte infiltration; low-level MCP-1 secretion with modest monocyte 
      infiltration resulted in tumor formation, whereas high secretion was associated 
      with massive monocyte/macrophage infiltration into the tumor mass, leading to its 
      destruction within a few days after injection into mice. Tumor growth stimulated 
      by monocytes/macrophages was due to increased angiogenesis. Vessel formation in 
      vitro was inhibited with mAbs against TNF-alpha, which, when secreted by 
      cocultures of melanoma cells with human monocytes, induced endothelial cells 
      under collagen gels to form branching, tubular structures. These studies 
      demonstrate that the biological effects of tumor-derived MCP-1 are biphasic, 
      depending on the level of secretion. This correlates with the degree of monocytic 
      cell infiltration, which results in increased tumor vascularization and TNF-alpha 
      production.
FAU - Nesbit, M
AU  - Nesbit M
AD  - The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
FAU - Schaider, H
AU  - Schaider H
FAU - Miller, T H
AU  - Miller TH
FAU - Herlyn, M
AU  - Herlyn M
LA  - eng
GR  - CA-10815/CA/NCI NIH HHS/United States
GR  - CA-25874/CA/NCI NIH HHS/United States
GR  - CA-80999/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Chemokine CCL2)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Cell Division/immunology
MH  - Cell Movement/immunology
MH  - Cell Survival/immunology
MH  - Cells, Cultured
MH  - Chemokine CCL2/biosynthesis/*physiology
MH  - Coculture Techniques
MH  - Dose-Response Relationship, Immunologic
MH  - Humans
MH  - Macrophages/immunology/pathology
MH  - Melanoma, Experimental/blood supply/*immunology/*pathology
MH  - Mice
MH  - Mice, SCID
MH  - Monocytes/*immunology/pathology
MH  - Neoplasm Transplantation
MH  - Neovascularization, Pathologic/immunology
MH  - Tumor Cells, Cultured/transplantation
MH  - Tumor Necrosis Factor-alpha/biosynthesis
EDAT- 2001/05/22 10:00
MHDA- 2001/08/17 10:01
CRDT- 2001/05/22 10:00
PHST- 2001/05/22 10:00 [pubmed]
PHST- 2001/08/17 10:01 [medline]
PHST- 2001/05/22 10:00 [entrez]
AID - 10.4049/jimmunol.166.11.6483 [doi]
PST - ppublish
SO  - J Immunol. 2001 Jun 1;166(11):6483-90. doi: 10.4049/jimmunol.166.11.6483.