Hyunjung Choi1, Sun Hee Jin2, Mi Hwa Han2, Jinyoung Lee3, Seyeon Ahn3, Minjeong Seong3, Hyun Choi1, Jiyeon Han1, Eun-Gyung Cho1, Tae Ryong Lee4, Minsoo Noh5. 1. Bioscience Research Institute, AmorePacific Corporation R&D Center, Yongin, Gyeonggi-do 446-729, Republic of Korea. 2. College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea; Natural Products Research Institute, Seoul National University, Seoul 151-742, Republic of Korea. 3. College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea. 4. Bioscience Research Institute, AmorePacific Corporation R&D Center, Yongin, Gyeonggi-do 446-729, Republic of Korea. Electronic address: trlee@amorepacific.com. 5. College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea; Natural Products Research Institute, Seoul National University, Seoul 151-742, Republic of Korea. Electronic address: minsoo@alum.mit.edu.
Abstract
BACKGROUND: The interactions between human epidermal melanocytes and their cellular microenvironment are important in the regulation of human melanocyte functions or in their malignant transformation into melanoma. Although the basement membrane extracellular matrix (BM-ECM) is one of major melanocyte microenvironments, the effects of BM-ECM on the human melanocyte functions are not fully explained at a molecular level. OBJECTIVE: This study was aimed to characterize the molecular and cellular interactions between normal human melanocytes (NHMs) and BM-ECM. METHODS: We investigated cell culture models of normal human melanocytes or melanoma cells on three-dimensional (3D) Matrigel to understand the roles of the basement membrane microenvironment in human melanocyte functions. Melanogenesis and melanobast biomarker expression in both primary human melanocytes and melanoma cells on 3D Matrigel were evaluated. RESULTS: We found that NHMs migrated and formed reversible paired box 3 (PAX3) expressing cell clusters on three-dimensional (3D) Matrigel. The melanogenesis was significantly decreased in the PAX3 expressing cell cluster. The expression profile of PAX3, SOX10, and MITF in the melanocyte cluster on 3D Matrigel was similar to that of melanoblasts. Interestingly, PAX3 and SOX10 showed an inverse expression profile in NHMs, whereas the inverse expression pattern of PAX3 and SOX10 was disrupted in melanoma MNT1 and WM266-4 cells. CONCLUSION: The human melanocyte culture on 3D Matrigel provides an alternative model system to study functions of human melanoblasts. In addition, this system will contribute to the elucidation of PAX3-related tumorigenic mechanisms to understand human melanoma.
BACKGROUND: The interactions between human epidermal melanocytes and their cellular microenvironment are important in the regulation of human melanocyte functions or in their malignant transformation into melanoma. Although the basement membrane extracellular matrix (BM-ECM) is one of major melanocyte microenvironments, the effects of BM-ECM on the human melanocyte functions are not fully explained at a molecular level. OBJECTIVE: This study was aimed to characterize the molecular and cellular interactions between normal human melanocytes (NHMs) and BM-ECM. METHODS: We investigated cell culture models of normal human melanocytes or melanoma cells on three-dimensional (3D) Matrigel to understand the roles of the basement membrane microenvironment in human melanocyte functions. Melanogenesis and melanobast biomarker expression in both primary human melanocytes and melanoma cells on 3D Matrigel were evaluated. RESULTS: We found that NHMs migrated and formed reversible paired box 3 (PAX3) expressing cell clusters on three-dimensional (3D) Matrigel. The melanogenesis was significantly decreased in the PAX3 expressing cell cluster. The expression profile of PAX3, SOX10, and MITF in the melanocyte cluster on 3D Matrigel was similar to that of melanoblasts. Interestingly, PAX3 and SOX10 showed an inverse expression profile in NHMs, whereas the inverse expression pattern of PAX3 and SOX10 was disrupted in melanoma MNT1 and WM266-4 cells. CONCLUSION: The human melanocyte culture on 3D Matrigel provides an alternative model system to study functions of human melanoblasts. In addition, this system will contribute to the elucidation of PAX3-related tumorigenic mechanisms to understand humanmelanoma.