Stem-cell origin of metastasis and heterogeneity in solid tumours.

An explanation for the inherently metastatic and heterogeneous nature of cancers may be their derivation from distinct stem cells. The type of stem cell from which a neoplasm arises determines both the metastatic potential and the phenotypic diversity of that neoplasm. Hence, tumours originating from an early stem cell or its progenitor cells metastasise readily and have a more heterogeneous phenotype, whereas tumours originating from a later stem cell or its progenitor cells have limited metastatic potential and a more homogeneous phenotype. Further investigation of the role of stem cells in the development of cancer may lead to the discovery of novel diagnostic tools, prognostic markers, and therapeutic targets in the battle against cancer.

[1]  U. Lendahl,et al.  Generalized potential of adult neural stem cells. , 2000, Science.

[2]  É. Mezey,et al.  Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[3]  E. Kohn,et al.  Heterogeneity of the motility responses in malignant tumor cells: A biological basis for the diversity and homing of metastatic cells , 1990, International journal of cancer.

[4]  A. Knudson Mutation and cancer in man , 1977 .

[5]  H. Blau,et al.  The Evolving Concept of a Stem Cell Entity or Function? , 2001, Cell.

[6]  L. Liotta,et al.  Biochemical mechanisms of tumor invasion and metastases. , 1988, Progress in clinical and biological research.

[7]  Neil D. Theise,et al.  Multi-Organ, Multi-Lineage Engraftment by a Single Bone Marrow-Derived Stem Cell , 2001, Cell.

[8]  L. B. Russell Genetic Mosaics and Chimeras in Mammals , 1978, Basic Life Sciences.

[9]  Masahiko Kuroda,et al.  Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development , 1998, Nature.

[10]  R. Alon,et al.  Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4. , 1999, Science.

[11]  S. Makino FURTHER EVIDENCE FAVORING THE CONCEPT OF THE STEM CELL IN ASCITES TUMORS OF RATS , 1955, Annals of the New York Academy of Sciences.

[12]  W. Sanger,et al.  Experimental evidence for the origin of ductal-type adenocarcinoma from the islets of Langerhans. , 1997, The American journal of pathology.

[13]  D. Solter,et al.  Embryo-derived teratocarcinomas elicit splenomegaly in syngeneic host , 1974, Nature.

[14]  W. F. Cox,et al.  The endodermal origin of the endocrine cells of an adenocarcinoma of the colon of the rat , 1982, Cancer.

[15]  Darwin J. Prockop,et al.  Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta , 1999, Nature Medicine.

[16]  G. B. Pierce,et al.  MULTIPOTENTIALITY OF SINGLE EMBRYONAL CARCINOMA CELLS. , 1964, Cancer research.

[17]  L. C. Stevens EXPERIMENTAL PRODUCTION OF TESTICULAR TERATOMAS IN MICE. , 1964, Proceedings of the National Academy of Sciences of the United States of America.

[18]  M. van de Rijn,et al.  Immunoblot analysis of CD34 expression in histologically diverse neoplasms. , 2000, The American journal of pathology.

[19]  N. Friedman The comparative morphogenesis of extragenital and gonadal teratoid tumors , 1951, Cancer.

[20]  Sidhu Gs The endodermal origin of digestive and respiratory tract APUD cells. Histopathologic evidence and a review of the literature. , 1979 .

[21]  V. Najfeld,et al.  Evidence for a multistep pathogenesis of chronic myelogenous leukemia. , 1981 .

[22]  W. Mars,et al.  Bone marrow as a potential source of hepatic oval cells. , 1999, Science.

[23]  Gideon Rechavi,et al.  A Possible Role for CXCR4 and Its Ligand, the CXC Chemokine Stromal Cell-Derived Factor-1, in the Development of Bone Marrow Metastases in Neuroblastoma1 , 2001, The Journal of Immunology.

[24]  D. Slamon,et al.  Expression of the c-kit proto-oncogene and its ligand stem cell factor (SCF) in normal and malignant human testicular tissue. , 1995, The Journal of urology.

[25]  S. Pathak Cytogenetic abnormalities in cancer: with special emphasis on tumor heterogeneity , 1990, Cancer and Metastasis Reviews.

[26]  Bingham Ja Letter: Lower oesophageal sphincter. , 1974 .

[27]  R. Mulligan,et al.  Dystrophin expression in the mdx mouse restored by stem cell transplantation , 1999, Nature.

[28]  G. Nicolson,et al.  Interactions of tumor cells with vascular endothelial cell monolayers: a model for metastatic invasion. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[29]  I. Weissman,et al.  Telomerase activity in hematopoietic cells is associated with self-renewal potential. , 1996, Immunity.

[30]  G Cossu,et al.  Muscle regeneration by bone marrow-derived myogenic progenitors. , 1998, Science.

[31]  A. Greenberg,et al.  The generation of tumor heterogeneity in vivo , 1980, International journal of cancer.

[32]  Y. Furukawa,et al.  Transcriptional repressor E2F-6 regulates apoptosis of hematopoietic stem cells , 2000 .

[33]  N. Skakkebæk,et al.  Heterogeneity of expression of immunohistochemical tumour markers in testicular carcinoma in situ: pathogenetic relevance , 1996, Virchows Archiv.

[34]  D. Arber,et al.  Paraffin section detection of the c-kit gene product (CD117) in human tissues: value in the diagnosis of mast cell disorders. , 1998, Human pathology.

[35]  Y. Nakamura,et al.  Genetic alterations during colorectal-tumor development. , 1988, The New England journal of medicine.

[36]  Pierce Gb,et al.  Embryonal carcinoma of the testis. , 1970 .

[37]  R. Motzer,et al.  Teratoma with malignant transformation: diverse malignant histologies arising in men with germ cell tumors. , 1998, The Journal of urology.

[38]  J. Gurdon,et al.  The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles. , 1962, Journal of embryology and experimental morphology.

[39]  V. Potter Phenotypic diversity in experimental hepatomas: the concept of partially blocked ontogeny. The 10th Walter Hubert Lecture. , 1978, British Journal of Cancer.

[40]  T. Mcclanahan,et al.  Involvement of chemokine receptors in breast cancer metastasis , 2001, Nature.

[41]  P. Humphrey,et al.  A transgenic mouse model of metastatic prostate cancer originating from neuroendocrine cells. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[42]  G. B. Pierce,et al.  Maturation arrest of stem cell differentiation is a common pathway for the cellular origin of teratocarcinomas and epithelial cancers. , 1994, Laboratory investigation; a journal of technical methods and pathology.

[43]  S. Baylin “APUD” cells fact and fiction , 1990, Trends in Endocrinology & Metabolism.

[44]  I. Fidler,et al.  Biological diversity in metastatic neoplasms: origins and implications. , 1982, Science.