Cooperative Autocrine and Paracrine Functions of Granulocyte Colony-Stimulating Factor and Granulocyte-Macrophage Colony-Stimulating Factor in the Progression of Skin Carcinoma Cells

Obermueller, Eva; Vosseler, Silvia; Fusenig, Norbert E.; Mueller, Margareta M.

doi:10.1158/0008-5472.can-03-3301

Cited by 106 publications

(122 citation statements)

References 48 publications

Supporting

Mentioning

116

Contrasting

Order By: Relevance

“…These cells represent an early stage of skin carcinogenesis because they harbor UVB type-specific p53 mutations (Lehman et al, 1993) as well as some chromosomal abnormalities typical for human skin SCCs (Lehman et al, 1993;Boukamp et al, 1997;Popp et al, 2002). While the HaCaT cells remained nontumorigenic through long-term passaging, they became tumorigenic by transduction with the Harvey-ras oncogene, increased temperature or stroma modulating growth factors known to be relevant for tumorigenicity (Boukamp et al, 1990b(Boukamp et al, , 1995(Boukamp et al, , 1997Skobe and Fusenig, 1998;Obermueller et al, 2004). Thus, the intrinsic stable nontumorigenic phenotype, together with the sensitivity for tumorigenic conversion upon distinct changes, make HaCaT cells a highly suitable model to study the role of UVA in skin carcinogenesis.…”

Section: Introductionmentioning

confidence: 99%

UVA radiation causes DNA strand breaks, chromosomal aberrations and tumorigenic transformation in HaCaT skin keratinocytes

et al. 2008

View full text Add to dashboard Cite

The role of UVA-radiation-the major fraction in sunlight-in human skin carcinogenesis is still elusive. We here report that different UVA exposure regime (4 Â 5 J/cm 2 per week or 1 Â 20 J/cm 2 per week) caused tumorigenic conversion (tumors in nude mice) of the HaCaT skin keratinocytes. While tumorigenicity was not associated with general telomere shortening, we found new chromosomal changes characteristic for each recultivated tumor. Since this suggested a nontelomere-dependent relationship between UVA irradiation and chromosomal aberrations, we investigated for alternate mechanisms of UVA-dependent genomic instability. Using the alkaline and neutral comet assay as well as c-H2AX foci formation on irradiated HaCaT cells (20-60 J/cm 2 ), we show a dosedependent and long lasting induction of DNA single and double (ds) strand breaks. Extending this to normal human skin keratinocytes, we demonstrate a comparable damage response and, additionally, a significant induction and maintenance of micronuclei (MN) with more acentric fragments (indicative of ds breaks) than entire chromosomes particularly 5 days post irradiation. Thus, physiologically relevant UVA doses cause long-lasting DNA strand breaks, a prerequisite for chromosomal aberration that most likely contribute to tumorigenic conversion of the HaCaT cells. Since normal keratinocytes responded similarly, UVA may likewise contribute to the complex karyotype characteristic for human skin carcinomas.

show abstract

Section: Introductionmentioning

confidence: 99%

UVA radiation causes DNA strand breaks, chromosomal aberrations and tumorigenic transformation in HaCaT skin keratinocytes

et al. 2008

View full text Add to dashboard Cite

show abstract

“…Several other significant GO terms such as ''chemotaxis'' and ''inflammatory response'' or ''chemokine receptor activity'' indicate paracrine effects leading to the recruiting of circulating cells, perhaps neutrophils to the invasion front. Macrophages, 51 neutrophilic granulocytes 52 and mast cells 53 have been shown to exhibit tumor-supporting effects. On the other hand, an inflammatory immune response is a well-known antitumor host reaction.…”

Section: Discussionmentioning

confidence: 99%

Global analysis of host tissue gene expression in the invasive front of colorectal liver metastases

Bandapalli

Geheeb

Kobelt

et al. 2005

Intl Journal of Cancer

View full text Add to dashboard Cite

Host cell reactions are a crucial determinant for tumor invasion. We analyzed on a genomewide scale gene expression differences between microdissected tissues taken from unaffected liver tissue of a human colorectal tumor (LS174) growing in the livers of nude mice and tissue from the host part of the invasive front. Due to the low degree of interspecies cross‐hybridization of 15% as determined on Affymetrix microarrays, our xenograft model allowed for the distinction of genes of murine versus human origin even if the respective tissues could not be isolated separately. Using the gene ontology (GO) classification, we were able to determine patterns of up‐ and downregulated genes in the liver part of the invasive front. We observed a pronounced overrepresentation, e.g., of the GO terms “extracellular matrix,” “cell communication,” “response to biotic stimulus,” “structural molecule activity” and “cell growth,” indicating a very pronounced host cell response to tumor invasion. On the single gene level, hepatic stellate cell (HSC) activation markers were overrepresented in the liver part of the invasion front. Immunohistochemistry and qPCR confirmed an activation of HSC as well as an increased number of HSC in the invasive front as compared to the noninvaded liver tissue. In summary, our data demonstrate the feasibility of an interspecies differential gene expression approach on a genomewide scale. © 2005 Wiley‐Liss, Inc.

show abstract

“…13 Although CSF2 was originally identified as a hematopoietic growth factor, 23 it has been shown to stimulate tumor growth and migration through an autocrine or paracrine mechanism. [24][25][26] A recent study demonstrates that CSF2 is secreted by senescent fibroblasts. 27 ELISA analysis was employed to measure the concentration of CSF2 in the conditioned media (CM) from irradiated MDA-MB-231-2A cells, and the results showed that CSF2 is release by senescent MDA-MB-231-2A cells (Fig.…”

Section: Csf2 Contributes To Radiation-induced Bystander Effects Via mentioning

confidence: 99%

Autophagy promotes radiation-induced senescence but inhibits bystander effects in human breast cancer cells

et al. 2014

View full text Add to dashboard Cite

Cooperative Autocrine and Paracrine Functions of Granulocyte Colony-Stimulating Factor and Granulocyte-Macrophage Colony-Stimulating Factor in the Progression of Skin Carcinoma Cells

Abstract: ABSTRACT

Cited by 106 publications

References 48 publications

UVA radiation causes DNA strand breaks, chromosomal aberrations and tumorigenic transformation in HaCaT skin keratinocytes

UVA radiation causes DNA strand breaks, chromosomal aberrations and tumorigenic transformation in HaCaT skin keratinocytes

Global analysis of host tissue gene expression in the invasive front of colorectal liver metastases

Autophagy promotes radiation-induced senescence but inhibits bystander effects in human breast cancer cells

Contact Info

Product

Resources

About