Without epithelial–mesenchymal transitions, in which polarized epithelial cells are converted into motile cells, multicellular organisms would be incapable of getting past the blastula stage of embryonic development. However, this important developmental programme has a more sinister role in tumour progression. Epithelial–mesenchymal transition provides a new basis for understanding the progression of carcinoma towards dedifferentiated and more malignant states.

Epithelial–mesenchymal transitions in tumour progression

Charge, Sophie B. P., and Michael A. Rudnicki. Cellular and Molecular Regulation of Muscle Regeneration. Physiol Rev 84: 209–238, 2004; 10.1152/physrev.00019.2003.—Under normal circumstances, mamma...

Cellular and Molecular Regulation of Muscle Regeneration

Hepatocyte growth factor/scatter factor and its receptor, the tyrosine kinase Met, arose late in evolution and are unique to vertebrates In spite of this, Met uses molecules such as Gab1 — homologues of which are present in Caenorhabditis elegans and Drosophila melanogaster — for downstream signalling Pivotal roles for Met in development and cancer have been established: Met controls cell migration and growth in embryogenesis; it also controls growth, invasion and metastasis in cancer cells; and activating Met mutations predispose to human cancer

Met, metastasis, motility and more

Hepatocyte growth factor (HGF) is a plasminogen-like protein thought to be a humoral mediator of liver regeneration A 145-kilodalton tyrosyl phosphoprotein observed in rapid response to HGF treatment of intact target cells was identified by immunoblot analysis as the beta subunit of the c-met proto-oncogene product, a membrane-spanning tyrosine kinase Covalent cross-linking of 125I-labeled ligand to cellular proteins of appropriate size that were recognized by antibodies to c-met directly established the c-met product as the cell-surface receptor for HGF

https://science.sciencemag.org/content/sci/251/4995/802.full.pdf

Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product

The present study demonstrates that fibroblasts associated with carcinomas stimulate tumor progression of initiated nontumorigenic epithelial cells both in an in vivo tissue recombination system and in an in vitro coculture system. Human prostatic carcinoma-associated fibroblasts grown with initiated human prostatic epithelial cells dramatically stimulated growth and altered histology of the epithelial population. This effect was not detected when normal prostatic fibroblasts were grown with the initiated epithelial cells under the same experimental conditions. In contrast, carcinoma-associated fibroblasts did not affect growth of normal human prostatic epithelial cells under identical conditions. From these data, we conclude that in this human prostate cancer model, carcinoma-associated fibroblasts stimulate progression of tumorigenesis. Thus, carcinoma-associated fibroblasts can direct tumor progression of an initiated prostate epithelial cell.

/pdf/carcinoma-associated-fibroblasts-direct-tumor-progression-of-15vju8hfwp.pdf

Carcinoma-associated fibroblasts direct tumor progression of initiated human prostatic epithelium.

Hepatocyte growth factor (HGF) is the most potent mitogen for mature parenchymal hepatocytes in primary culture, and seems to be a hepatotrophic factor that acts as a trigger for liver regeneration after partial hepatectomy and liver injury. The partial purification and characterization of HGF have been reported. We have demonstrated that pure HGF from rat platelets is a new growth factor effective at concentrations as low as 1 ng ml-1. The effects of HGF and epidermal growth factor (EGF) are additive. The activity of HGF is not species-specific, although it does not stimulate growth in Swiss 3T3 fibroblasts. HGF has a relative molecular mass (Mr) of 82,000 and is a heterodimer composed of a large alpha-subunit of Mr 69,000 and a small beta-subunit of Mr 34,000. Here we report the amino-acid sequence of human HGF determined by complementary DNA cloning and the expression of biologically active human HGF from COS-1 cells transfected with cloned cDNA. The nucleotide sequence of the human HGF cDNA reveals that both alpha- and beta-chains are contained in a single open reading frame coding for a pre-pro precursor protein of 728 amino acids.

Molecular cloning and expression of human hepatocyte growth factor

Multiple growth factors synergistically stimulate proliferation of primitive hematopoietic progenitor cells. A human myeloid cell line, KPB-M15, constitutively produces a novel hematopoietic cytokine, termed stem cell growth factor (SCGF), possessing species-specific proliferative activities. Here we report the molecular cloning, expression, and characterization of a cDNA encoding human SCGF using a newly developed λSHDM vector that is more efficient for differential and expression cloning. cDNA for SCGF encodes a 29-kDa polypeptide without N-linked glycosylation. SCGF transiently produced by COS-1 cells supports growth of hematopoietic progenitor cells through a short-term liquid culture of bone marrow cells and exhibits promoting activities on erythroid and granulocyte/macrophage progenitor cells in primary semisolid culture with erythropoietin and granulocyte/macrophage colony-stimulating factor, respectively. Expression of SCGF mRNA is restricted to myeloid cells and fibroblasts, suggesting that SCGF is a growth factor functioning within the hematopoietic microenvironment. SCGF could disclose some human-specific mechanisms as yet unidentified from studies on the murine hematopoietic system.

https://www.pnas.org/content/pnas/94/14/7577.full.pdf

Cloning, expression, and characterization of a cDNA encoding a novel human growth factor for primitive hematopoietic progenitor cells

A novel polypeptide exhibiting a growth promoting activity on hematopoietic stem cells; a gene encoding this polypeptide; an antibody reacting specifically with the polypeptide; a process for isolating the above-mentioned gene; and a vector to be used in this process Thus, the pathologies of various hemopoietic organ diseases caused by abnormalities in hematopoietic cells and bone marrow inhibition can be clarified and, in its turn, these diseases can be diagnosed or treated Also, it becomes possible to amplify hematopoietic cells in vitro for marrow graft required in treating these diseases or to elevate the gene transfer efficiency into hematopoietic stem cells for gene utilization Moreover, the above-mentioned process and vector for isolating the SCGF gene are applicable to the clarification of other novel genes and thus contribute to the development of genetic engineering techniques

Hematopoietic stem cell growth factor (SCGF)

Human stem cell growth factor (SCGF) produced by a myeloid cell line, KPB-M15, exhibits species-specific hematopoietic activities. However, KPB-M15-conditioned medium induced colony formation of mouse

A Human Myeloid Cell Line Producing Stem Cell Growth Factor, KPB-M15, Secretes Another Growth Factor Active on Murine Hematopoietic Progenitor Cells

L'invention a pour objet un polypeptide de type nouveau actif en tant que facteur de croissance sur des cellules souches hematopoietiques; un gene codant ce polypeptide; un anticorps reagissant specifiquement audit polypeptide; un procede d'isolement du gene susmentionne; et un vecteur a utiliser dans le cadre de ce procede. En apportant des eclaircissements sur les pathologies de diverses maladies organiques dues a des anomalies de cellules hematopoietiques ou a une inhibition medullaire osseuse, ledit polypeptide permet de diagnostiquer ou de traiter ces maladies. Il offre egalement la possibilite d'amplifier les cellules hematopoietiques in vitro lorsque le traitement desdites maladies necessite une greffe de la moelle ou lorsqu'il convient d'accroitre l'efficacite du transfert de genes dans des cellules souches hematopoietiques, en vue d'une utilisation genique. En outre, le procede susmentionne et le vecteur isolant le gene du facteur de croissance des cellules souches hematopoietiques servent a definir d'autres genes nouveaux et contribuent ainsi au developpement des techniques de genie genetique.

Atsushi Sugimura

Papers

Molecular cloning and expression of human hepatocyte growth factor

Cloning, expression, and characterization of a cDNA encoding a novel human growth factor for primitive hematopoietic progenitor cells

Hematopoietic stem cell growth factor (SCGF)

A Human Myeloid Cell Line Producing Stem Cell Growth Factor, KPB-M15, Secretes Another Growth Factor Active on Murine Hematopoietic Progenitor Cells

Facteur de croissance des cellules souches hematopoietiques (scgf)