Extensive characterization of sphere models established from colorectal cancer cell lines

Links between cancer and stem cells have been proposed for many years. As the cancer stem cell (CSC) theory became widely studied, new methods were developed to culture and expand cancer cells with conserved determinants of “stemness”. These cells show increased ability to grow in suspension as spheres in serum-free medium supplemented with growth factors and chemicals. The physiological relevance of this phenomenon in established cancer cell lines remains unclear. Cell lines have traditionally been used to explore tumor biology and serve as preclinical models for the screening of potential therapeutic agents. Here, we grew cell-forming spheres (CFS) from 25 established colorectal cancer cell lines. The molecular and cellular characteristics of CFS were compared to the bulk of tumor cells. CFS could be isolated from 72 % of the cell lines. Both CFS and their parental CRC cell lines were highly tumorigenic. Compared to their parental cells, they showed similar expression of putative CSC markers. The ability of CRC cells to grow as CFS was greatly enhanced by prior treatment with 5-fluorouracil. At the molecular level, CFS and parental CRC cells showed identical gene mutations and very similar genomic profiles, although microarray analysis revealed changes in CFS gene expression that were independent of DNA copy-number. We identified a CFS gene expression signature common to CFS from all CRC cell lines, which was predictive of disease relapse in CRC patients. In conclusion, CFS models derived from CRC cell lines possess interesting phenotypic features that may have clinical relevance for drug resistance and disease relapse.     

Intracellular localization of alpha-fetoprotein and serum albumin in the central nervous system of the rat during fetal and postnatal development]

The morphological localisation of alphafetoprotein (AFP), serumalbumin (SA), transferrin and immunoglobulins (IgG) has been studied in the developing central nervous system of the Rat by immunocytochemical methods. Evidence is presented of a highly selective staining for AFP and SA, both proteins exhibiting the same topographical distribution. Practically all the areas of the brain and the spinal cord are stained at a given moment of the developmental process. The labeling is cytoplasmic and in the neuronal elements extends to their axonic and dendritic prolongations. The localization of AFP and SA in the nervous system may be related to the well known binding properties of these proteins for varied substances (estrogen and/or fatty acids). The morphological data presented here suggest that both proteins may be actively involved in the uptake of such substances by the cellular structures of the nervous tissue.