Platelet extracts induce growth, migration and invasion in human hepatocellular carcinoma in vitro.
BACKGROUND
Thrombocytopenia has been reported to be associated with small size HCCs, and thrombocytosis to be associated with large size HCCs. The aim was to examine the effects of platelets in relation to HCC cell growth.


METHODS
The effects of time-expired pooled normal human platelets were examined on human HCC cell line growth and invasion.


RESULTS
Blood platelet numbers increased with increasing HCC tumor size and portal vein invasion. Platelet extracts enhanced cell growth in 4 human HCC cell lines, as well as cell migration, medium AFP levels and decreased apoptosis. Cell invasion was significantly enhanced, using a Matrigel-coated trans-well membrane and 3D (Real-Time Imaging) invasion assay. Western blots showed that platelets caused enhanced phospho-ERK and phospho-JNK signaling and anti-apoptotic effect with increase of Bcl-xL (anti-apoptotic marker) and decrease of Bid (pro-apoptotic marker) levels. Their growth effects were blocked by a JNK inhibitor.


CONCLUSIONS
Platelets stimulated growth and invasion of several HCC cell lines in vitro, suggesting that platelets or platelet growth factors could be a potential pharmacological target.
Laboratory of biochemistry and tumor biology, National Institute for Digestive Diseases, IRCCS 'Saverio de Bellis', via Turi 27, 70013 Castellana Grotte, BA, Italy. brianicarr@hotmail.com.
Brian I
BI
Carr
Aldo
A
Cavallini
Rosalba
R
D'Alessandro
Maria Grazia
MG
Refolo
Catia
C
Lippolis
Antonio
A
Mazzocca
Caterina
C
Messa
D017209:Apoptosis; D001792:Blood Platelets / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D015398:Signal Transduction; D018874:Spheroids, Cellular; D014407:Tumor Cells, Cultured