Characterization of tumorigenic sub-lines from a poorly tumorigenic human colon-adenocarcinoma cell line.
The interaction of tumor cells with extracellular-matrix components is suspected to play an important role in tumorigenesis induction. The tumorigenicity of a poorly tumorigenic human colon-adenocarcinoma cell line (BCS-TC2) was induced by co-injection with Matrigel. A new cell sub-line, BCS-TC2.1, was isolated and established from these tumors. Implantation of these cells in nude mice in the absence of Matrigel-generated tumors which allowed the establishment of another tumorigenic cell sub-line, BCS-TC2.2. Matrigel and laminin, but not collagens, promote the tumorigenicity of BCS-TC2 cells, probably due to specific interactions of a pre-existing minor cell sub-population with laminin, which facilitate the initial growth of these cells in vivo. Cytogenetic analysis reveals that both sub-lines originate from the parental one, but a new marker in chromosome 9 is observed. These sub-lines present a lower degree of differentiation, as deduced from the lower CEA content, 5'-nucleotidase and alkaline-phosphatase activities. No variation is observed in the mRNA and protein expression of the 67-kDa laminin-binding protein. However, an increase in beta1 integrins and a parallel decrease in beta4 integrin were detected. Thus, the new sub-lines, compared to the parental cells, present karyotypic and phenotypic differences such as the expression of a distinctive integrin pattern. This system represents a useful model for understanding the development and progression of tumorigenicity in cancer cells.
López-Conejo
T
T
Departamento de Bioquímica y Biologia Molecular, Facultad de Químicas, Universidad Complutense, Madrid, Spain.
Olmo
N
N
Turnay
J
J
Navarro
J
J
Lizarbe
A
A
D015720:5'-Nucleotidase / Q000378:metabolism; D000230:Adenocarcinoma / Q000473:pathology*; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000473:pathology*; D004338:Drug Combinations; D005109:Extracellular Matrix / Q000502:physiology*; D006801:Humans; D016023:Integrins / Q000378:metabolism; D007797:Laminin / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011509:Proteoglycans / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D017474:Receptors, Laminin / Q000235:genetics; D014407:Tumor Cells, Cultured
D002272:Carcinoembryonic Antigen; D004338:Drug Combinations; D016023:Integrins; D007797:Laminin; D011509:Proteoglycans; D012333:RNA, Messenger; D017474:Receptors, Laminin; C059485:matrigel; D003094:Collagen; D000469:Alkaline Phosphatase; D015720:5'-Nucleotidase