PMID- 16267016
OWN - NLM
STAT- MEDLINE
DCOM- 20051222
LR  - 20091119
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 65
IP  - 21
DP  - 2005 Nov 1
TI  - Induction of hepatocyte growth factor/scatter factor by fibroblast clustering 
      directly promotes tumor cell invasiveness.
PG  - 9914-22
AB  - For determining the malignant behavior of a tumor, paracrine interactions between 
      stromal and cancer cells are crucial. We previously reported that fibroblast 
      clustering induces cyclooxygenase-2 (COX-2), plasminogen activation, and 
      programmed necrosis, all of which were significantly reduced by nonsteroidal 
      anti-inflammatory drugs (NSAID). We have now found that tumor cell-conditioned 
      medium induces similar fibroblast clustering. Activation of the necrotic pathway 
      in clustering fibroblasts, compared with control monolayer cultures, induced a 
      massive >200-fold production of bioactive hepatocyte growth factor/scatter factor 
      (HGF/SF), which made human carcinoma cells spread and invade a collagen lattice. 
      This response occurred only if a functional, properly processed c-Met receptor 
      was present, which was then rapidly phosphorylated. The invasion-promoting 
      activity was inhibited by a neutralizing HGF/SF antibody. NSAIDs, if added early 
      during fibroblast aggregation, inhibited HGF/SF production effectively but had no 
      effect at later stages of cell aggregation. Our results thus provide the first 
      evidence that aggravated progression of tumors with necrotic foci may involve 
      paracrine reciprocal signaling leading to stromal activation by direct cell-cell 
      contact (i.e., nemosis).
FAU - Kankuri, Esko
AU  - Kankuri E
AD  - Institute of Biomedicine, Pharmacology, Haartman Institute, University of 
      Helsinki, Finland. esko.kankuri@helsinki.fi
FAU - Cholujova, Dana
AU  - Cholujova D
FAU - Comajova, Monika
AU  - Comajova M
FAU - Vaheri, Antti
AU  - Vaheri A
FAU - Bizik, Jozef
AU  - Bizik J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Culture Media, Conditioned)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
SB  - IM
MH  - Anti-Inflammatory Agents, Non-Steroidal/pharmacology
MH  - Carcinoma/metabolism/pathology
MH  - Cell Aggregation/physiology
MH  - Cell Line, Tumor
MH  - Cell Movement/physiology
MH  - Culture Media, Conditioned
MH  - Fibroblasts/*cytology/drug effects/*metabolism
MH  - Hepatocyte Growth Factor/*biosynthesis
MH  - Humans
MH  - Melanoma/metabolism/pathology
MH  - Neoplasm Invasiveness
MH  - Neoplasms/*metabolism/*pathology
MH  - Proto-Oncogene Proteins c-met/biosynthesis
MH  - Spheroids, Cellular
MH  - Stromal Cells/cytology
EDAT- 2005/11/04 09:00
MHDA- 2005/12/24 09:00
CRDT- 2005/11/04 09:00
PHST- 2005/11/04 09:00 [pubmed]
PHST- 2005/12/24 09:00 [medline]
PHST- 2005/11/04 09:00 [entrez]
AID - 65/21/9914 [pii]
AID - 10.1158/0008-5472.CAN-05-1559 [doi]
PST - ppublish
SO  - Cancer Res. 2005 Nov 1;65(21):9914-22. doi: 10.1158/0008-5472.CAN-05-1559.