PMID- 10072259
OWN - NLM
STAT- MEDLINE
DCOM- 19990318
LR  - 20191102
IS  - 0022-2143 (Print)
IS  - 0022-2143 (Linking)
VI  - 133
IP  - 3
DP  - 1999 Mar
TI  - Tumor necrosis factor-alpha stimulates attachment of small cell lung carcinoma to 
      endothelial cells.
PG  - 265-73
AB  - Tumor cell attachment to endothelial cells (ECs) is an important step in the 
      metastasis of small cell lung carcinoma (SCLC). Tumor necrosis factor-alpha 
      (TNF-alpha) stimulation of ECs increases the attachment of some malignant cell 
      types to ECs by affecting the expression of cell adhesion molecules (CAMs). 
      Similarly, the inhibition of EC protein kinase C (PKC) and tyrosine kinase (TK) 
      pathways modulates TNF-alpha-mediated effects on CAM expression. We hypothesized 
      that TNF-alpha would increase SCLC attachment to ECs by affecting CAM expression 
      through activation of PKC and TK pathways. To test this hypothesis, human 
      umbilical vein endothelial cells (HUVECs) were stimulated with TNF-alpha (0 to 
      500 U/mL) for variable time periods (1 to 24 hours), and the attachment of H82 
      cells (an SCLC cell line) to the HUVECs was quantified. TNF-alpha stimulation of 
      the HUVECs increased H82 attachment from 28.1% +/- 1.6% to 48.8% +/- 1.7% (P < 
      .05). Preincubation of HUVECs with the PKC inhibitors bis-indolylmaleimide (BIN) 
      or calphostin C or the TK inhibitors genistein or herbimycin A (HMA) blocked the 
      TNF-alpha-induced increase in H82 cell attachment. The addition of antibodies to 
      vitronectin (Vn) or beta1-integrin to TNF-alpha-activated HUVECs before the 
      addition of the H82 cells also significantly decreased H82 attachment, whereas 
      the addition of antibodies to E-selectin, P-selectin, vascular cell adhesion 
      molecule (VCAM), intercellular adhesion molecule (ICAM), neural cell adhesion 
      molecule (NCAM), sialyl-Lewis(x), fibronectin (Fn), alpha(v)-integrin, 
      alpha3-integrin, alpha4-integrin, or alpha5-integrin had no effect on SCLC 
      attachment. In summary, the TNF-alpha-mediated increase in SCLC attachment to ECs 
      appears to be mediated by the activation of EC PKC and TK pathways as well as 
      through effects on the function or expression of EC Vn and beta1 integrin.
FAU - Sheski, F D
AU  - Sheski FD
AD  - Department of Medicine, Indiana University School of Medicine, Indianapolis, USA.
FAU - Natarajan, V
AU  - Natarajan V
FAU - Pottratz, S T
AU  - Pottratz ST
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Lab Clin Med
JT  - The Journal of laboratory and clinical medicine
JID - 0375375
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Chromium Radioisotopes)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Integrins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Vitronectin)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.11.13 (Protein Kinase C)
SB  - IM
MH  - Carcinoma, Small Cell/*pathology
MH  - *Cell Adhesion
MH  - Cell Adhesion Molecules/physiology
MH  - Cell Survival
MH  - Cells, Cultured
MH  - Chromium Radioisotopes
MH  - Endothelium, Vascular/*pathology
MH  - Enzyme Inhibitors/pharmacology
MH  - Humans
MH  - Integrins/antagonists & inhibitors/physiology
MH  - Kinetics
MH  - Lung Neoplasms/*pathology
MH  - Protein Kinase C/antagonists & inhibitors
MH  - Protein-Tyrosine Kinases/antagonists & inhibitors
MH  - Recombinant Proteins
MH  - Tumor Cells, Cultured
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - Umbilical Veins
MH  - Vitronectin/antagonists & inhibitors/physiology
EDAT- 1999/03/11 00:00
MHDA- 1999/03/11 00:01
CRDT- 1999/03/11 00:00
PHST- 1999/03/11 00:00 [pubmed]
PHST- 1999/03/11 00:01 [medline]
PHST- 1999/03/11 00:00 [entrez]
AID - S0022-2143(99)90083-5 [pii]
AID - 10.1016/s0022-2143(99)90083-5 [doi]
PST - ppublish
SO  - J Lab Clin Med. 1999 Mar;133(3):265-73. doi: 10.1016/s0022-2143(99)90083-5.