Logo of brjcancerBJC HomepageBJC Advance online publicationBJC Current IssueSubmitting an article to BJCWeb feeds
Br J Cancer. Jul 1978; 38(1): 1–23.
PMCID: PMC2009671

Phenotypic diversity in experimental hepatomas: the concept of partially blocked ontogeny. The 10th Walter Hubert Lecture.

Abstract

Cancer cells should be seen not as exclusively a problem in cell proliferation, but rather as a problem combining the processes of proliferation and differentiation, hence the phrase introduced in 1968: "oncogeny is blocked ontogeny". Cancer tissues resemble foetal tissues in many ways but they differ from foetal tissue in being unable to "recapitulate the total programme leading to an orchestrated collection of organism-serving cells" that are programmed "to make the organ as adaptive as possible to the range of environmental variations in which it evolved". Citing the "Osgood Principle" from the 1950's, recent supporting evidence was described, in which the most mature differentiated cells exert positive and negative feedback upon the proliferation of their progenitor stem cells. Advanced examples in the haemopoietic series were drawn from the work of Sachs, Metcalf, Till and McCulloch, and Kurland and Moore. The blocked ontogeny hypothesis was further elaborated in the concept of "partially-blocked ontogeny", which is intended to describe a situation in which highly differentiated slowly growing tumours contain some cells which have left the proliferating pool to differentiate along the normal pathway, but are blocked somewhere short of the final organism-serving state, in harmony with earlier suggestions by Osgood, by Pierce, and by Sachs.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (3.2M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Abramson S, Miller RG, Phillips RA. The identification in adult bone marrow of pluripotent and restricted stem cells of the myeloid and lymphoid systems. J Exp Med. 1977 Jun 1;145(6):1567–1579. [PMC free article] [PubMed]
  • Alexander P. Foetal "antigens" in cancer. Nature. 1972 Jan 21;235(5334):137–140. [PubMed]
  • BECKER AJ, McCULLOCH EA, TILL JE. Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. Nature. 1963 Feb 2;197:452–454. [PubMed]
  • Bradley TR, Metcalf D. The growth of mouse bone marrow cells in vitro. Aust J Exp Biol Med Sci. 1966 Jun;44(3):287–299. [PubMed]
  • BROOKE JH, OSGOOD EE. Long-term mixed cultures of human hemic cells, with granulocytic, lymphocytic, plasmocytic and erythrocytic series represented. Blood. 1959 Jul;14(7):803–815. [PubMed]
  • Broxmeyer HE, Baker FL, Galbraith PR. In vitro regulation of granulopoiesis in human leukemia: application of an assay for colony-inhibiting cells. Blood. 1976 Mar;47(3):389–402. [PubMed]
  • Broxmeyer HE, Moore MA, Ralph P. Cell-free granulocyte colony inhibiting activity derived from human polymorphonuclear neutrophils. Exp Hematol. 1977 Mar;5(2):87–102. [PubMed]
  • Butcher FR, Potter VR. Control of the adenosine 3',5'-monophosphate-adenyl cyclase system in the livers of developing rats. Cancer Res. 1972 Oct;32(10):2141–2147. [PubMed]
  • Butcher FR, Scott DF, Potter VR, Morris HP. Endocrine control of cyclic adenosine 3',5'-monophosphate levels in several Morris hepatomas. Cancer Res. 1972 Oct;32(10):2135–2140. [PubMed]
  • Cohen P. The subunit structure of rabbit-skeletal-muscle phosphorylase kinase, and the molecular basis of its activation reactions. Eur J Biochem. 1973 Apr 2;34(1):1–14. [PubMed]
  • CRONE M, ITZHAKI S. ON THE RELATIVE FUNCTIONING OF THE PATHWAYS FOR FORMATION OF THYMIDINE NUCLEOTIDES IN THE REGNERATING LIVER AND SPLEEN OF THE RAT. Biochim Biophys Acta. 1965 Jan 11;95:8–13. [PubMed]
  • de Néchaud B, Uriel J. Antigènes cellulaires transitoires du foie de rat. I. Sécrétion et synthèse des protéines sériques foetospécifiques au cours du développement et de la régénération hépatiques. Int J Cancer. 1971 Jul 15;8(1):71–80. [PubMed]
  • Fibach E, Hayashi M, Sachs L. Control of normal differentiation of myeloid leukemic cells to macrophages and granulocytes. Proc Natl Acad Sci U S A. 1973 Feb;70(2):343–346. [PMC free article] [PubMed]
  • Gorman RR, Bunting S, Miller OV. Modulation of human platelet adenylate cyclase by prostacyclin (PGX). Prostaglandins. 1977 Mar;13(3):377–388. [PubMed]
  • Greengard P. Phosphorylated proteins as physiological effectors. Science. 1978 Jan 13;199(4325):146–152. [PubMed]
  • Gruber DF, Zucali JR, Mirand EA. Identification of erythropoietin producing cells in fetal mouse liver cultures. Exp Hematol. 1977 Sep;5(5):392–398. [PubMed]
  • HECHT LI, POTTER VR. Nucleic acid metabolism in regenerating rat liver. III. Intermediates in the synthesis of DNA pyrimidine nucleotides. Cancer Res. 1956 Nov;16(10 Pt 1):999–1004. [PubMed]
  • Holliday R, Pugh JE. DNA modification mechanisms and gene activity during development. Science. 1975 Jan 24;187(4173):226–232. [PubMed]
  • Kelley DS, Potter VR. Amino acid concentrating ability of slowly growing autochthonous hepatomas and host livers. Biochem Biophys Res Commun. 1977 Mar 21;75(2):219–225. [PubMed]
  • Korn AP, Henkelman RM, Ottensmeyer FP, Till JE. Investigations of a stochastic model of haemopoiesis. Exp Hematol. 1973;1(6):362–375. [PubMed]
  • Kroes R, Sontag JM, Sell S, Williams GM, Weisburger JH. Elevated concentrations of serum alpha-fetoprotein in rats with chemically induced liver tumors. Cancer Res. 1975 May;35(5):1214–1217. [PubMed]
  • Kurland JI, Bockman RS, Broxmeyer HE, Moore MA. Limitation of excessive myelopoiesis by the intrinsic modulation of macrophage-derived prostaglandin E. Science. 1978 Feb 3;199(4328):552–555. [PubMed]
  • Kurland J, Moore MA. Modulation of hemopoiesis by prostaglandins. Exp Hematol. 1977 Sep;5(5):357–373. [PubMed]
  • Laishes BA, Roberts E, Farber E. In vitro measurement of carcinogen-resistant liver cells during hepatocarcinogenesis. Int J Cancer. 1978 Feb 15;21(2):186–193. [PubMed]
  • Leffert HL, Koch KS, Rubalcava B. Present paradoxes in the environmental control of hepatic proliferation. Cancer Res. 1976 Nov;36(11 Pt 2):4250–4255. [PubMed]
  • Lotem J, Sachs L. Different blocks in the differentiation of myeloid leukemic cells. Proc Natl Acad Sci U S A. 1974 Sep;71(9):3507–3511. [PMC free article] [PubMed]
  • McCulloch EA, Mak TW, Price GB, Till JE. Organization and communication in populations of normal and leukemic hemopoietic cells. Biochim Biophys Acta. 1974 Dec 31;355(3-4):260–299. [PubMed]
  • Maeda S, Sachs L. Control of normal differentiation of myeloid leukemic cells. XIII. Inducibility for some stages of differentiation by dimethylsulfoxide and its disassociation from inducibility by MGI. J Cell Physiol. 1978 Feb;94(2):181–185. [PubMed]
  • MALEY F, MALEY GF. Nucleotide interconversions. II. Elevation of deoxycytidylate deaminase and thymidylate synthetase in regenerating rat liver. J Biol Chem. 1960 Oct;235:2968–2970. [PubMed]
  • MALEY F, MALEY GF. Nucleotide interconversions. IV. Activities of deoxycytidylate deaminase and thymidylate synthetase in normal rat liver and hepatomas. Cancer Res. 1961 Nov;21:1421–1426. [PubMed]
  • Metcalf D. Regulation of granulocyte and monocyte-macrophage proliferation by colony stimulating factor (CSF): a review. Exp Hematol. 1973;1(4):185–201. [PubMed]
  • OSGOOD EE. A unifying concept of the etiology of the leukemias, lymphomas, and cancers. J Natl Cancer Inst. 1957 Feb;18(2):155–166. [PubMed]
  • OSGOOD EE, KRIPPAEHNE ML. The gradient tissue culture method. Exp Cell Res. 1955 Aug;9(1):116–127. [PubMed]
  • Pace-Asciak CR. Oxidative biotransformations of arachidonic acid. Prostaglandins. 1977 May;13(5):811–817. [PubMed]
  • Pariza MW, Butcher FR, Kletzien RF, Becker JE, Potter VR. Induction and decay of glucagon-induced amino acid transport in primary cultures of adult rat liver cells: paradoxical effects of cycloheximide and puromycin. Proc Natl Acad Sci U S A. 1976 Dec;73(12):4511–4515. [PMC free article] [PubMed]
  • Pitot HC, Barsness L, Goldsworthy T, Kitagawa T. Biochemical characterisation of stages of hepatocarcinogenesis after a single dose of diethylnitrosamine. Nature. 1978 Feb 2;271(5644):456–458. [PubMed]
  • PITOT HC, POTTER VR. An enzymic study on the cellular origin of the Dunning and the Novikoff hepatomas in the rat. Biochim Biophys Acta. 1960 Jun 3;40:537–539. [PubMed]
  • Pluznik DH, Sachs L. The cloning of normal "mast" cells in tissue culture. J Cell Physiol. 1965 Dec;66(3):319–324. [PubMed]
  • Pluznik DH, Sachs L. The induction of clones of normal mast cells by a substance from conditioned medium. Exp Cell Res. 1966 Oct;43(3):553–563. [PubMed]
  • POTTER VR. Guest editorial: a plea for formal support for study and reflection. Cancer Res. 1956 Sep;16(8):725–727. [PubMed]
  • POTTER VR. MODELS AS AIDS TO COMMUNICATION. Natl Cancer Inst Monogr. 1964 Apr;13:111–116. [PubMed]
  • Potter VR. Recent trends in cancer biochemistry: the importance of studies on fetal tissue. Proc Can Cancer Conf. 1969;8:9–30. [PubMed]
  • Reynolds RD, Scott DF, Potter VR, Morris HP. Induction of tyrosine aminotransferase and amino acid transport in Morris hepatomas and in adult and neonatal rat liver. Cancer Res. 1971 Nov;31(11):1580–1589. [PubMed]
  • Scott DF, Butcher FR, Potter VR, Morris HP. Naturally occurring and induced levels of amino acid transport and tyrosine aminotransferase in rats bearing Morris hepatomas. Cancer Res. 1972 Oct;32(10):2127–2134. [PubMed]
  • Sell S, Morris HP. Relationship of rat alpha 1-fetoprotein to growth rate and chromosome composition of Morris hepatomas. Cancer Res. 1974 Jun;34(6):1413–1417. [PubMed]
  • Sell S, Nichols M, Becker FF, Leffert HL. Hepatocyte proliferation and alpha 1-fetoprotein in pregnant, neonatal, and partially hepatectomized rats. Cancer Res. 1974 Apr;34(4):865–871. [PubMed]
  • Senn JS, McCulloch EA, Till JE. Comparison of colony-forming ability of normal and leukaemic human marrow in cell culture. Lancet. 1967 Sep 16;2(7516):597–598. [PubMed]
  • Sneider TW, Potter VR. Deoxycytidylate deaminase and related enzymes of thymidine triphosphate metabolism in hepatomas and precancerous rat liver. Adv Enzyme Regul. 1969;7:375–394. [PubMed]
  • Sneider TW, Potter VR, Morris HP. Enzymes of thymidine triphosphate synthesis in selected Morris hepatomas. Cancer Res. 1969 Jan;29(1):40–54. [PubMed]
  • Stanley ER, Hansen G, Woodcock J, Metcalf D. Colony stimulating factor and the regulation of granulopoiesis and macrophage production. Fed Proc. 1975 Dec;34(13):2272–2278. [PubMed]
  • Steel GG, Adams K, Barrett JC. Analysis of the cell population kinetics of transplanted tumours of widely-differing growth rate. Br J Cancer. 1966 Dec;20(4):784–800. [PMC free article] [PubMed]
  • Stephenson JR, Axelrad AA, McLeod DL, Shreeve MM. Induction of colonies of hemoglobin-synthesizing cells by erythropoietin in vitro. Proc Natl Acad Sci U S A. 1971 Jul;68(7):1542–1546. [PMC free article] [PubMed]
  • Stöcker E, Heine WD. Regeneration of liver parenchyma under normal and pathological conditions. Beitr Pathol. 1971;144(4):400–408. [PubMed]
  • TILL JE, McCULLOCH EA. A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat Res. 1961 Feb;14:213–222. [PubMed]
  • TILL JE, MCCULLOCH EA, SIMINOVITCH L. A STOCHASTIC MODEL OF STEM CELL PROLIFERATION, BASED ON THE GROWTH OF SPLEEN COLONY-FORMING CELLS. Proc Natl Acad Sci U S A. 1964 Jan;51:29–36. [PMC free article] [PubMed]
  • Walker PR, Potter VR. Isozyme studies on adult, regenerating, precancerous and developing liver in relation to findings in hepatomas. Adv Enzyme Regul. 1972;10:339–364. [PubMed]
  • Watabe H, Hirai H, Sato H. -Fetoprotein in rats transplanted with ascites hepatoma. Gan. 1972 Apr;63(2):189–199. [PubMed]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...