title: Human melanocytes form a PAX3-expressing melanocyte cluster on Matrigel by the cell migration process.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Bioscience Research Institute, AmorePacific Corporation R&D Center, Yongin, Gyeonggi-do 446-729, Republic of Korea.
authors.forename: Hyunjung
authors.initials: H
authors.lastname: Choi
authors.affiliation: 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.
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Jin
authors.affiliation: 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.
authors.forename: Mi Hwa
authors.initials: MH
authors.lastname: Han
authors.affiliation: College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Jinyoung
authors.initials: J
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Seyeon
authors.initials: S
authors.lastname: Ahn
authors.affiliation: College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Minjeong
authors.initials: M
authors.lastname: Seong
authors.affiliation: Bioscience Research Institute, AmorePacific Corporation R&D Center, Yongin, Gyeonggi-do 446-729, Republic of Korea.
authors.forename: Hyun
authors.initials: H
authors.lastname: Choi
authors.affiliation: Bioscience Research Institute, AmorePacific Corporation R&D Center, Yongin, Gyeonggi-do 446-729, Republic of Korea.
authors.forename: Jiyeon
authors.initials: J
authors.lastname: Han
authors.affiliation: Bioscience Research Institute, AmorePacific Corporation R&D Center, Yongin, Gyeonggi-do 446-729, Republic of Korea.
authors.forename: Eun-Gyung
authors.initials: EG
authors.lastname: Cho
authors.affiliation: Bioscience Research Institute, AmorePacific Corporation R&D Center, Yongin, Gyeonggi-do 446-729, Republic of Korea. Electronic address: trlee@amorepacific.com.
authors.forename: Tae Ryong
authors.initials: TR
authors.lastname: Lee
authors.affiliation: 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.
authors.forename: Minsoo
authors.initials: M
authors.lastname: Noh
mesh_terms: D001485:Basement Membrane / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D003094:Collagen / Q000737:chemistry*; D004338:Drug Combinations; D005109:Extracellular Matrix / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D007797:Laminin / Q000737:chemistry*; D008543:Melanins / Q000737:chemistry; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism*; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism*; D010858:Pigmentation; D011509:Proteoglycans / Q000737:chemistry*; D055757:SOXE Transcription Factors / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D004338:Drug Combinations; D007797:Laminin; C497234:MITF protein, human; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051761:Paired Box Transcription Factors; D011509:Proteoglycans; C527923:SOX10 protein, human; D055757:SOXE Transcription Factors; C059485:matrigel; D003094:Collagen
keywords: Human melanocytes; Matrigel; Melanoblast; Melanocyte cluster; Melanoma; PAX3