title: Why do we not all die of cancer at an early age?
abstract: Traditionally, surveillance against cancer was thought of as mainly immunological. With the exception of tumors with a clear viral involvement, such as immunoblastomas (Epstein-Barr virus, EBV), cervical, anogenital, and skin carcinomas (HPV), and Kaposi's sarcoma (HHV-8) where the immune system is confronted with virally encoded, nonself targets, tumors with no viral involvement provide poor targets. Attempts to influence them by immunological means are akin to the breaking of tolerance. Robust nonimmunological surveillance mechanisms include DNA repair-based checkpoint functions, and the triggering of growth arrest and/or apoptosis pathways by DNA damage or by illegitimate oncogene activation (intracellular surveillance). There is emerging evidence for epigenetic surveillance, reflected in the stringency of imprinting. A fourth mechanism, intercellular surveillance, or microenvironmental control, is rapidly gaining momentum. It can be mediated by contactual controls or by differentiation-inducing signals. Somatic hybridization experiments have shown that tumorigenicity is usually suppressed in somatic hybrids between normal and malignant cells, as long as a fairly complete chromosome complement is maintained. Individual normal cell-derived chromosomes may have a similar suppressive effect. For example, genetic and molecular dissection of human 3p that shows frequent deletions in many human tumors has identified multiple tumor suppressor genes, which can inhibit both in vitro growth and in vivo tumorigenicity. In addition, five genes were found with an "asymmetric activity," capable of suppressing tumorigenicity, without affecting in vitro growth. These genes, LTF, L1MD1, HYAL1, HYAL2, and VHL, are of particular interest because they may be involved in microenvironmental control.
authors: Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden.
authors: George
authors: G
authors: Klein
authors: Stefan
authors: S
authors: Imreh
authors: Eugene R
authors: ER
authors: Zabarovsky
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D004260:DNA Repair / Q000502:physiology*; D044127:Epigenesis, Genetic / Q000502:physiology*; D006801:Humans; D009369:Neoplasms / Q000235:genetics*
chemical_list: D051017:Apoptosis Regulatory Proteins