A new type of cancer cell growth
Re: cancer stem cells.
We have shown that such cells have he potential to undergo neosis, a parasexual, somatic reduction division characterized by karyokinesis via nuclear budding followed by asymmetric cytokinesis, giving rise to aneuploid or near diploid daughter cells termed Raju cells (Raju means king or leader in the Telugu language). The latter cells are unique in that they transiently display stem cell properties, have inherited genomic instability, have the potential to differentiate into tumor cells and have extended, but, limited mitotic division potential. At the end of their mitotic life span, they repeat the cycle of senescence, neosis and production of the next generation of Raju cells, which repeat the same cycle of events several times through the life of the tumor. When we expose tumor cells to chemotherapeutic agents or radiation, they undergo premature senescence, and some of them escape senescence via neosis, and produce Raju cells that are resistance to genotoxis.
Thus, neosis is the escape mechanism from senescence that gives rise to tumor cells which may become resistant to therapy and that yields the aneuploid cells characteristic of solid tumors. The discovery of neosis therefore questions the basic principles of our current concept of cancer, namely that cancers arise via mitosis, that cancer cells are immortal, and that cancer cell continuity is due to the unlimited asymmetric mitotic division potential of mutant stem cells or cancer stem cells. We think instead that cancer arises via neosis, cancer cells are not immortal but undergo repeated senescent phases, and that tumor cell continuity is due to the escape from senescent phase, since tumor cells carry mutant genes in the senescence checkpoint pathway.
Our data supports the view that genesis and regenesis of Raju cells via repetitive neotic divisions is responsible for the origin and continuous growth of different types of tumors. This accommodates the role of telomerase in tumor growth, explains a role for the ectopic expression of meiotic genes in tumor cells, and also for the first time explains the role of senescent cells that are found in tumors in vivo and in vitro. We invite others to verify our findings.
Halifax, Nova Scotia, Canada
References1. I. Weissman, M. Clarke, "Leukemia and cancer stem cells," The Scientist, 20(4):35, April 2006.2. P. Dirks, "Stem cells for brain cancer," The Scientist, 20(4):37, April 2006.3. M. Sundaram et al., "Neosis: a novel type of cell division in cancer," Cancer Biol Ther, 3:217-8 2004.4. R. Rajaraman et al., "Neosis - a paradigm of self-renewal in cancer," Cell Biol Int 29:1084-97, 2005.
The problem with microarrays
Re: "In search of microarray standards."
Vanderbilt-Ingram Cancer Center
References1. J. Perkel, "In search of micrarray standards," The Scientist, 20(3):73, March 2006.2. P. Liang, A.B. Pardee. "Analysing differential gene expression in cancer," Nat Review Cancer, 3:869-76, 2003.
The interactome: Next steps
Re: "Time for a Human Interactome Project?"
We have suggested a comparative functional genomic approach to the problem of identifying gene regulatory networks, which would then be amenable to '-omics.' By determining ligand/receptor signaling pathways common to development, homeostasis and repair across phyla
John S. Torday
Harbor-UCLA Medical Center Campus