The inhibition of tumor cell adhesion on human mesothelial cells (HOMC) by phospholipids in vitro.
OBJECTIVE
Intraperitoneal tumor cell adhesion to extracellular matrix and to mesothelial cells mediated by integrins is an important step in developing peritoneal carcinosis. In former animal studies, we could demonstrate that intraperitoneal treatment with a new phospholipid (PL) emulsion significantly reduces the amount of peritoneal carcinosis by adhesion prevention. This in vitro study tries to elucidate the influence of phospholipids on cells of the human gastric cancer cell line (NUGC-4) and the human rectal cancer cell line (HRT-18) adhering to mesothelial cells (HOMC) in a monolayer culture in vitro.


METHODS
HOMC cells were derived from omentum majus from patients undergoing elective abdominal surgery. Three passages of both cancer cell lines (NUGC-4 and HRT-18) were used. 1x10(5)/100 microl (HRT-18) or 1.2x10(5)/100 microl (NUGC-4) cells, according to forgoing dilution series, were pretreated with different concentrations of phospholipid emulsion (0.05, 0.1, 0.5, 0.75, 1% PL) stained with cell tracker chloromethyl-benzamidodialkylcarbocyanine (CM-DIL) and seeded into each well on the mesothelial monolayer. After 90 min, the number of adherent cells was counted by fluorescence microscopy at 530 and 620 nm. Additionally, flow cytometric analysis of integrin alpha3 and beta1 expression on the tumor cell surface after treatment with phospholipids was completed.


RESULTS
We found a dose dependent effect of phospholipids on both tumor cell lines causing a reduction of cell-cell adhesion. Already low concentrations of phospholipids (PL 0.5) had a significant influence. The mean cell count could be reduced from 234+/-12/mm2 in controls to 124+/-41/mm2 (PL 0.5; NUG-4) and from 295+/-49/mm2 to 169+/-29/mm2 (PL 0.5; HRT-18), respectively. Additionally, the integrin alpha3 and beta1 expression on both cell lines could be reduced.


CONCLUSIONS
Our results within the scope of published data indicate that adhesion prevention is capable to reduce peritoneal carcinosis.
Jansen
M
M
Department of Surgery, University Clinic, RWTH Aachen, Pauwelsstr. 30, 52057, Aachen, Germany. mjansen@ukaachen.de
Jansen
P Lynen
PL
Otto
J
J
Kirtil
T
T
Neuss
S
S
Treutner
K-H
KH
Schumpelick
V
V
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004655:Emulsions; D004848:Epithelium / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D039001:Integrin alpha Chains / Q000096:biosynthesis; D039641:Integrin beta Chains / Q000096:biosynthesis; D010534:Peritoneal Neoplasms / Q000517:prevention & control* / Q000556:secondary; D010743:Phospholipids / Q000494:pharmacology*; D012004:Rectal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
D016588:Anticarcinogenic Agents; D004655:Emulsions; D039001:Integrin alpha Chains; D039641:Integrin beta Chains; D010743:Phospholipids