Hyeong-Sun Moon

Melanocyte Stem Cell Activation and Translocation Initiate Cutaneous Melanoma in Response to UV Exposure

Melanoma is one of the deadliest cancers, yet the cells of origin and mechanisms of tumor initiation remain unclear. The majority of melanomas emerge from clear skin without a precursor lesion, but it is unknown whether these melanomas can arise from melanocyte stem cells (MCSCs). Here we employ mouse models to define the role of MCSCs as melanoma cells of origin, demonstrate that MCSC quiescence acts as a tumor suppressor, and identify the extrinsic environmental and molecular factors required for the critical early steps of melanoma initiation. Specifically, melanomas originate from melanoma-competent MCSCs upon stimulation by UVB, which induces MCSC activation and translocation via an inflammation-dependent process. Moreover, the chromatin-remodeling factor Hmga2 in the skin plays a critical role in UVB-mediated melanomagenesis. These findings delineate melanoma formation from melanoma-competent MCSCs following extrinsic stimuli, and they suggest that abrogation of Hmga2 function in the microenvironment can suppress MCSC-originating cutaneous melanomas.

Evaluation of serum cystatin-C and symmetric dimethylarginine concentrations in dogs with heart failure from chronic mitral valvular insufficiency

Reduction in glomerular filtration rate (GFR) is a common complication in advanced stages of heart failure (HF). The convenient and precise assessment for GFR would be useful for early detection of renal impairment in HF dogs. Our hypothesis of this study was the GFR would be reduced in advanced stages of HF from chronic mitral valvular insufficiency (CMVI), as indicated by renal markers including serum cystatin-C (Cys-C) and symmetric dimethylarginine (SDMA) concentrations. Forty-three client-owned dogs consisting of 33 dogs with different stages of HF from CMVI and 10 age-matched healthy dogs were enrolled in this study. Serum Cys-C and SDMA concentrations along with other renal (i.e., urea nitrogen and creatinine) and echocardiographic markers were evaluated in healthy and CMVI dogs. Serum Cys-C concentrations were 1.4 ± 0.4 mg/l in control, 2.1 ± 0.9 mg/l in ISACHC I, 2.9 ± 0.8 mg/l in ISACHC II and 3.6 ± 0.6 mg/l in ISACHC III dogs, whereas serum SDMA concentrations were 8 ± 2 µg/dl in control, 14 ± 3 µg/dl in ISACHC I, 18 ± 6 µg/dl in ISACHC II and 22 ± 7 µg/dl in ISACHC III dogs. There was close correlation of serum Cys-C and SDMA concentrations to serum creatinine, urea nitrogen and the severity of HF. Our study demonstrated that the GFR was decreased in dogs with CMVI having earlier stages of HF.

Understanding Cancer Cells of Origin in Cutaneous Tumors

Identifying the cellular origin of each cancer represents a major challenge in biology, primarily due to the vast cellular and molecular heterogeneity found in their subtypes. Nevertheless, defining the physiological conditions and the molecular mechanisms through which a tumor initiates from its cancer cell(s) of origin (CCO) is indispensable in designing strategies for cancer prevention, early detection and effective treatment. In recent years, significant progress has been made in unraveling the cellular origin of a number of cancer types through lineage tracing in genetically engineered mouse models. Although the cell of origin for primary tumors is becoming more apparent, the origin of cancer stem cells and their relationship to the original CCO is presently unclear. In this chapter, we will review the recently elucidated CCOs and mechanisms of tumor initiation in the most common forms of cancer; cutaneous basal and squamous cell carcinoma.

A path from melanocyte stem cells to cutaneous melanoma illuminated by UVB

ABSTRACT The relationship between melanocyte stem cells (MCSCs) and melanoma has been unclear. We recently demonstrated that melanoma-prone MCSCs are able to initiate cutaneous melanoma following stem cell activation through ultraviolet-B (UVB) exposure or natural stem cell cycling. Conversely, MCSC quiescence is sufficient to suppress tumorigenesis. This provides new insight into the role of environmental factors in tumor initiation from adult stem cells.