Development and Characterization of a Novel in vitro Progression Model for UVB-Induced Skin Carcinogenesis
Nikhil Tyagi,Arun Bhardwaj,Sanjeev K. Srivastava,Sumit Arora,Saravanakumar Marimuthu,Sachin Kumar Deshmukh,Ajay P. Singh,James E. Carter,Seema Singh +8 more
TL;DR: It is demonstrated that UVB-transformed HaCaT cells gain enhanced proliferation rate, apoptosis-resistance, and colony- and sphere-forming abilities in a progressive manner, and these derived cells are able to form aggressive squamous cell carcinoma upon inoculation into the nude mice, while parental Ha CaT cells remain non-tumorigenic.
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Abstract: Epidemiological studies suggest ultraviolet B (UVB) component (290-320 nm) of sun light is the most prevalent etiologic factor for skin carcinogenesis--a disease accounting for more than two million new cases each year in the USA alone. Development of UVB-induced skin carcinoma is a multistep and complex process. The molecular events that occur during UVB-induced skin carcinogenesis are poorly understood largely due to the lack of an appropriate cellular model system. Therefore, to make a progress in this area, we have developed an in vitro model for UVB-induced skin cancer using immortalized human epidermal keratinocyte (HaCaT) cells through repetitive exposure to UVB radiation. We demonstrate that UVB-transformed HaCaT cells gain enhanced proliferation rate, apoptosis-resistance, and colony- and sphere-forming abilities in a progressive manner. Moreover, these cells exhibit increased aggressiveness with enhanced migration and invasive potential and mesenchymal phenotypes. Furthermore, these derived cells are able to form aggressive squamous cell carcinoma upon inoculation into the nude mice, while parental HaCaT cells remain non-tumorigenic. Together, these novel, UVB-transformed progression model cell lines can be very helpful in gaining valuable mechanistic insight into UVB-induced skin carcinogenesis, identification of novel molecular targets of diagnostic and therapeutic significance, and in vitro screening for novel preventive and therapeutic agents.
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References
Tumorigenic conversion of immortal human keratinocytes through stromal cell activation.
Mihaela Skobe,Norbert E. Fusenig +1 more
TL;DR: It is demonstrated that an activated stromal environment can promote tumorigenic conversion of nontumorigenic keratinocytes by inducing sustained epithelial hyperproliferation, apparently caused by a dual action of PDGF-BB.
266
•Journal Article
c-Ha-ras oncogene expression in immortalized human keratinocytes (HaCaT) alters growth potential in vivo but lacks correlation with malignancy.
TL;DR: In this article, the c-Ha-ras (EJ) oncogene was transfected with spontaneous immortalized human skin keratinocytes (HaCaT) via a plasmid construct which also contained the selectable neomycin gene.
223
Sustained nontumorigenic phenotype correlates with a largely stable chromosome content during long-term culture of the human keratinocyte line HaCat
Petra Boukamp,Susanne Popp,Susanne Altmeyer,Andrea Hülsen,Clare L. Fasching,Thomas Cremer,Norbert E. Fusenig +6 more
TL;DR: The data suggest that multiple changes often correlated with a “transformed phenotype,” including extensive karyotypic alterations and mutational inactivation of TP53, are well compatible with a nontumorigenic phenotype of the HaCaT cells, and that preserved chromosomal balance may be crucial for this stability during long‐term propagation.
151
No end in sight: the skin cancer epidemic continues
TL;DR: Recognizing the NMSC epidemic is critical as the incidence-and cost-will continue to increase.
149