EurekaMag
+ Translate
+ Most Popular
The pigeon tick (Argas reflexus): its biology, ecology, and epidemiological aspects
Prevalence of hemoglobin abnormalities in Kebili (Tunisian South)
Lipogranuloma: a preventable complication of dacryocystorhinostomy
Value of basal plasma cortisol assays in the assessment of pituitary-adrenal insufficiency
Bees from the Belgian Congo. The acraensis group of Anthophora
Placing gingival retraction cord
Total serum IgE, allergy skin testing, and the radioallergosorbent test for the diagnosis of allergy in asthmatic children
Acariens plumicoles Analgesoidea parasites des oiseaux du Maroc
Injuries of terminal phalanges of the fingers in children
Biology of flowering and nectar production in pear (Pyrus communis)
Das Reliktvorkommen der Aspisviper (Vipera aspis L.) im Schwarzwald
Hydrological modelling of drained blanket peatland
Pathologic morphology and clinical significance of the anomalous origin of the left circumflex coronary artery from the right coronary artery. General review and autopsy analysis of 30 cases
Cyto genetic analyses of lymphocyte cultures after exposure to calcium cyclamate
Axelrodia riesei, a new characoid fish from Upper Rio Meta in Colombia With remarks concerning the genus Axelrodia and description of a similar, sympatric, Hyphessobrycon-species
Favorable evolution of a case of tuberculosis of pancreas under antibiotic action
RIFM fragrance ingredient safety assessment, Valencene, CAS Registry Number 4630-07-3
Parenteral microemulsions: an overview
Temperate pasture: management for grazing and conservation
Evaluation of a new coprocessed compound based on lactose and maize starch for tablet formulation
Thermal expansion and cracking of three confined water-saturated igneous rocks to 800C
Revision of the genera of the tribe Stigmoderini (Coleoptera: Buprestidae) a discussion of phylogenetic relationships
Anal tuberculosis. Report of a case
Gastric tuberculosis in the past and present
Adaptive responses of the cardiovascular system to prolonged spaceflight conditions: assessment with Holter monitoring

Tumor progression of skin carcinoma cells in vivo promoted by clonal selection, mutagenesis, and autocrine growth regulation by granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor


Tumor progression of skin carcinoma cells in vivo promoted by clonal selection, mutagenesis, and autocrine growth regulation by granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor



American Journal of Pathology 159(4): 1567-1579



ISSN/ISBN: 0002-9440

PMID: 11583982

DOI: 10.1016/s0002-9440(10)62541-2

Tumor microenvironment is crucial for cancer growth and progression as evidenced by reports on the significance of tumor angiogenesis and stromal cells. Using the HaCaT/HaCaT-ras human skin carcinogenesis model, we studied tumor progression from benign tumors to highly malignant squamous cell carcinomas. Progression of tumorigenic HaCaT-ras clones to more aggressive and eventually metastatic phenotypes was reproducibly achieved by their in vivo growth as subcutaneous tumors in nude mice. Their enhanced malignant phenotype was stably maintained in recultured tumor cells that represented, identified by chromosomal analysis, a distinct subpopulation of the parental line. Additional mutagenic effects were apparent in genetic alterations involving chromosomes 11 and 2, and in amplification and overexpression of the H-ras oncogene. Importantly, in vitro clonal selection of benign and malignant cell lines never resulted in late-stage malignant clones, indicating the importance of the in vivo environment in promoting an enhanced malignant phenotype. Independently of their H-ras status, all in vivo-progressed tumor cell lines (five of five) exhibited a constitutive and stable expression of the hematopoietic growth factors granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor, which may function as autocrine/paracrine mediators of tumor progression in vivo. Thus, malignant progression favored by the in vivo microenvironment requires both clonal selection of subpopulations adapted to in vivo growth and mutational events leading to stable functional alterations.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 011599458

Download citation: RISBibTeXText

Related references

Cooperative autocrine and paracrine functions of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor in the progression of skin carcinoma cells. Cancer Research 64(21): 7801-7812, 2004

Autocrine growth regulation by granulocyte colony-stimulating factor and granulocyte macrophage colony-stimulating factor in human gliomas with tumor progression. American Journal of Pathology 155(5): 1557-1567, 1999

Cytotoxicity of white blood cells activated by granulocyte-colony-stimulating factor, granulocyte/macrophage-colony-stimulating factor and macrophage-colony-stimulating factor against tumor cells in the presence of various monoclonal antibodies. Cancer Immunology Immunotherapy: Cii 39(4): 254-262, 1994

Transcriptional rates of granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, interleukin-3, and macrophage colony-stimulating factor genes in activated cord versus adult mononuclear cells: alteration in cytokine expression may be secondary to posttranscriptional instability. Pediatric Research 34(5): 560-564, 1993

Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor promote malignant growth of cells from head and neck squamous cell carcinomas in vivo. Cancer Research 66(16): 8026-8036, 2006

The proliferative effects of human granulocyte macrophage colony stimulating factor alpha and granulocyte macrophage colony stimulating factor beta and murine granulocyte colony stimulating factor in microwell cultures of fractionated human marrow cells. Leukemia Research 9(5): 521-528, 1985

Thrombin stimulates synthesis of macrophage colony-stimulating factor, granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor by human proximal tubular epithelial cells in culture. Nephron Extra 2(1): 1-8, 2012

Opposite effect of tumor necrosis factor alpha on granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor-dependent growth of normal and leukemic hemopoietic progenitors. Cancer Research 50(16): 5065-5071, 1990

Opposite effect of tumor necrosis factor α on granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor-dependent growth of normal and leukemic hemopoietic progbenitors. Cancer Research (Baltimore) 50(16): 5065-5071, 1990

Effects on spleen colony-forming unit self-renewal after retroviral-mediated gene transfer of multi-colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, or granulocyte colony-stimulating factor. Experimental Hematology 19(7): 602-607, 1991

Quantitative cell-cycle progression analysis of the first three successive cell cycles of granulocyte colony-stimulating factor and/or granulocyte-macrophage colony-stimulating factor-stimulated human CD34+ bone marrow cells in relation to their colony formation. Blood 81(12): 3211-3216, 1993

Therapeutic use of cytokines to modulate phagocyte function for the treatment of infectious diseases: current status of granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, macrophage colony-stimulating factor, and interferon-gamma. Journal of Infectious Diseases 185(10): 1490-1501, 2002

A randomized trial comparing the combination of granulocyte-macrophage colony-stimulating factor plus granulocyte colony-stimulating factor versus granulocyte colony-stimulating factor for mobilization of dendritic cell subsets in hematopoietic progenitor cell products. Biology of Blood and Marrow Transplantation: Journal of the American Society for Blood and Marrow Transplantation 10(12): 848-857, 2004

Taxol induces the hematopoietic growth factor granulocyte-macrophage colony-stimulating factor in murine B-cells by stabilization of granulocyte-macrophage colony-stimulating factor nuclear RNA. Cancer Research 54(15): 4150-4154, 1994

Cyclooxygenase-2 inhibitor NS-398 suppresses cell growth and constitutive production of granulocyte-colony stimulating factor and granulocyte macrophage-colony stimulating factor in lung cancer cells. Cancer Science 94(2): 173-180, 2003