New Advances in the Chemistry and Biology of Organized Growth

Needham, Joseph

doi:10.1177/003591573602901209

Cited by 50 publications

(39 citation statements)

References 89 publications

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“…Some 50 years ago, Needham [29] and Waddington [30] speculated that cancers represented an escape from morphogenetic field like those which guide embryonic development. A similar statement has been recently put forward again by Simon, who suggest that "any change that leads stem cells to escape from the niche [i.e., the morphogenetic field] would result in tumor formation" [31].…”

Section: The Morphogenetic Field and Reversal Of The Cancer Phenotypementioning

confidence: 99%

Embryonic Morphogenetic Field Induces Phenotypic Reversion in Cancer Cells. Review Article

Bizzarri¹,

Cucina²,

Biava³

et al. 2011

curr pharm biotechnol

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Cancer cells introduced into developing embryos can be committed to a complete reversion of their malignant phenotype. It is unlikely that such effects could be ascribed to only few molecular components interacting according to a simple linear-dynamics model, and they claim against the somatic mutation theory of cancer. Some 50 years ago, Needham and Waddington speculated that cancer represents an escape from morphogenetic field like those which guide embryonic development. Indeed, disruption of the morphogenetic field of a tissue can promote the onset as well as the progression of cancer. On the other hand, placing tumor cells into a "normal" morphogenetic field - like that of an embryonic tissue - one can reverse malignant phenotype, "reprogramming" tumor into normal cells. According to the theoretical framework provided by the thermodynamics of dissipative systems, morphogenetic fields could be considered as distinct attractors, to which cell behaviors are converging. Cancer-attractors are likely positioned somewhat close to embryonic-attractors. Indeed, tumors share several morphological and ultra-structural features with embryonic cells. The recovering of an "embryonic-like" cell shape might enable the gene regulatory network to reactivate embryonic programs, and consequently to express antigenic and biochemical embryonic characters. This condition confers to cancer an unusual sensitivity to embryonic regulatory cues. Thus, it is not surprising that cancer cells exposed to specific embryonic morphogenetic fields undergoes significant modifications, eventually leading to a complete phenotypic reversion.

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Section: The Morphogenetic Field and Reversal Of The Cancer Phenotypementioning

confidence: 99%

Embryonic Morphogenetic Field Induces Phenotypic Reversion in Cancer Cells. Review Article

Bizzarri¹,

Cucina²,

Biava³

et al. 2011

curr pharm biotechnol

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“…Figure 5 summarizes our current, speculative scheme for the overall mechanism of action of angiogenin as it relates to angiogenesis outlined here: (1) angiogenin first binds to a cellular receptor through its cell binding region. (2) This activates phospholipases C and A2, among others, with consequent second messenger signal transduction, the details of which have not been elucidated. In addition, angiogenin is (3) endocytosed, and (4) undergoes translocation to the nucleus.…”

Section: Mechanism Of Actionmentioning

confidence: 99%

“…before long and would serve as a road map for biology throughout the remainder of the millennium. Needham, in particular, raised hopes for great events to come [2]. However, his optimism seemed exaggerated since progress actually was quite slow.…”

Section: Introductionmentioning

confidence: 99%

Organogenesis and angiogenin

Vallée

Riordan

1997

CMLS, Cell. mol. life sci.

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Our search for an angiogenesis-inducing factor in culture medium conditioned by human colon adenocarcinoma cells (HT-29) was inspired by the 'organizer' hypothesis originally postulated by Spemann. It led us to the isolation of angiogenin, a 14 kD protein homologous to pancreatic ribonuclease and one of the most potent stimulators of blood vessel formation known. This review summarizes the properties of angiogenin, its enzymatic and three-dimensional relationship to ribonuclease A (RNase A), those aspects of its structure that are critical for its biological function, and the therapeutic potential of angiogenin inhibition. Despite having the same arrangement of catalytic residues as RNase A, angiogenin has very low enzymatic activity. It lacks one of the four disulphide loops of RNase A; instead, the corresponding residues form part of a cell binding region. Both the catalytic activity and cell binding site are essential for angiogenesis. Angiogenin binds to cell-surface actin in confluent endothelial cells and to an as yet uncharacterized receptor on proliferating cells. Internalization and translocation to the nucleolus are also required for activity. Inhibitors of angiogenin can block angiogenesis in vitro and prevent tumour growth in vivo. Thus, a noncytotoxic neutralizing monoclonal antibody prevents the establishment of HT-29 human tumour xenografts in up to 65% of treated athymic mice. In those tumours that develop, the number of vascular elements is reduced. Actin also prevents the establishment of tumours while exhibiting no toxic effects at daily doses > 50 times the molar amount of circulating mouse angiogenin. These antagonists also inhibit the appearance of tumours derived from two other human tumour cell lines. Inhibition of the action of angiogenin may prove to be an effective therapeutic approach for the treatment of malignant disease.

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“…The morphogenetic field became the basic paradigm of embryology. In the 1930s, Needham (1936) and Waddington (1935) proposed that neoplastic development resulted from alterations of the normal interactions that occur in those morphogenetic fields. In other words, carcinogens, as teratogens-i.e., agents that interfere with normal embryonic development-would disrupt the normal dynamic interaction of neighboring cells and tissues both during early development and throughout adulthood.…”

Section: An Organicist View Of Carcinogenesis: the Tissue Organizatiomentioning

confidence: 99%

“…The TOFT postulates that carcinogens act initially by disrupting the normal, reciprocal interactions that take place among cells in the stroma and parenchyma (usually an epithelium) of an organ (Waddington, 1935;Needham, 1936;Orr, 1958;Sonnenschein & Soto, 2000). This disruption results in a lessening of the cells' ability to "read" their positional and historical background.…”

Section: Biological Complexity and Emergencementioning

confidence: 99%

Emergentism by default: A view from the bench

Soto

Sonnenschein

2006

Synthese

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For the last 50 years the dominant stance in experimental biology has been reductionism in general, and genetic reductionism in particular. Philosophers were the first to realize that the belief that the Mendelian genes were reduced to DNA molecules was questionable. Soon, experimental data confirmed these misgivings. The optimism of molecular biologists, fueled by early success in tackling relatively simple problems has now been tempered by the difficulties encountered when applying the same simple ideas to complex problems. We analyze three examples taken from experimental data that illustrate the shortcomings of this sort of reductionism. In the first, alterations in the expression of a large number of genes coexist with normal phenotypes at supra-cellular levels of organization; in the second, the supposed intrinsic specificity of hormonal signals is negated; in the third, the notion that cancer is a cellular problem caused by mutated genes is challenged by data gathered both from the reductionist viewpoint and the alternative view proposing that carcinogenesis is development gone awry. As an alternative to reductionism, we propose that the organicist view is a good starting point from which to explore these phenomena. However, new theoretical concepts are needed to grapple with the apparent circular causality of complex biological phenomena.

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New Advances in the Chemistry and Biology of Organized Growth

Cited by 50 publications

References 89 publications

Embryonic Morphogenetic Field Induces Phenotypic Reversion in Cancer Cells. Review Article

Embryonic Morphogenetic Field Induces Phenotypic Reversion in Cancer Cells. Review Article

Organogenesis and angiogenin

Emergentism by default: A view from the bench

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