Comparative study of T84 and T84SF human colon carcinoma cells: in vitro and in vivo ultrastructural and functional characterization of cell culture and metastasis.
To better understand the relationship between tumor heterogeneity, differentiation, and metastasis, suitable experimental models permitting in vitro and in vivo studies are necessary. A new variant cell line (T84SF) exhibiting an altered phenotype was recently selected from a colon cancer cell line (T84) by repetitive plating on TNF-alpha treated human endothelial cells and subsequent selection for adherent cells. The matched pair of cell lines provides a useful system to investigate the extravasation step of the metastatic cascade. Since analysis of morphological differences can be instructive to the understanding of metastatic potential of tumor cells, we compared the ultrastructural and functional phenotype of T84 and T84SF cells in vitro and in vivo. The reported ultrastructural features evidence differences between the two cell lines; selected cells showed a marked pleomorphism of cell size and nuclei, shape, and greater surface complexity. These morphological differences were also coupled with biochemical data showing a distinct tyrosine phosphorylation-based signaling, an altered localization of beta-catenin, MAPK, and AKT activation, as well as an increased expression in T84SF cells of Bcl-X(L), a major regulator of apoptosis. Therefore, these cell lines represent a step forward in the development of appropriate models in vitro and in vivo to investigate colon cancer progression.
Alessandro
Riccardo
R
Dipartimento di Biopatologia e Metodologie Biomediche, Sezione di Biologia e Genetica, Università di Palermo, Via Divisi 83, 90133 Palermo, Italy. ricale@unipa.it
Di Bella
Maria Antonietta
MA
Flugy
Anna Maria
AM
Fontana
Simona
S
Damiani
Francesca
F
Corrado
Chiara
C
Colomba
Paolo
P
Todaro
Matilde
M
Russo
Domenica
D
Santoro
Alessandra
A
Kohn
Elise C
EC
De Leo
Giacomo
G
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor / Q000378:metabolism / Q000473:pathology*; D002467:Cell Nucleus / Q000648:ultrastructure; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D022162:Cytoplasmic Vesicles / Q000201:enzymology / Q000648:ultrastructure; D018450:Disease Progression; D018093:Gelatinases / Q000378:metabolism; D006801:Humans; D046529:Microscopy, Electron, Transmission; D009362:Neoplasm Metastasis / Q000473:pathology*; D010641:Phenotype; D015398:Signal Transduction; D051020:bcl-X Protein / Q000378:metabolism
C494811:BCL2L1 protein, human; D014408:Biomarkers, Tumor; D051020:bcl-X Protein; D018093:Gelatinases