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Topic Report Skin Cell Reporter: 謝宗勳 Advisor: 黃升龍 2012/03/22 Outline • Cell Type in Skin – – – – – – Keratinocyte SCC BCC Melanoma Melanocyte Fibroblast • Cell Line – – – – – – HaCaT A431 BCC-1/KMC A2058 A-375 Hs68 • Summary 2 Cell Type in Skin • The skin has 2 main layers: – Epidermis,表皮 (upper or outer layer) – Dermis,真皮 (lower or inner layer) • Type of cell line we have: – Epidermis • • • • • Keratinocyte Squamous cell carcinoma Basal cell carcinoma Melanoma Melanocyte – Dermis • Fibroblast • There are 3 types of skin cancer: – Squamous cell carcinoma (SCC) – Basal cell carcinoma (BCC) – Melanoma 3 Malignancy (惡性) • Malignancy in cancers is characterized by anaplasia (逆 行性生長), invasiveness, and metastasis (遠端轉移). – Anaplasia, NC ratio is 1:1 – Normal cell, NC ratio is 1:4 or 1:6 Melanoma Nonmelanoma 4 Keratinocyte (角質細胞) • Keratinocyte is the predominant cell type in the epidermis, the outermost layer of the skin, constituting 95% of the cells found there. 角質層 透明層 顆粒層 [Ca+] [Ca+] 棘層 基底層 [Ca+] 5 Function of Keratinocyte Corneocytes: have flattened out and are composed mainly of keratin protein responsible for maintaining the integrity and hydration of the skin Reduce friction and shear forces between the stratum corneum and stratum granulosum 1. lost their nucleus and cytoplasmic organelles 2. keratin proteins and water-proofing lipids are being produced and organized Basal keratinocytes responsible for renewing epidermal cells Prickle cell synthesize keratin 6 Squamous Cancer Cell (鱗癌細胞) • Begins in squamous cells. (Squamous cells are found in the tissue that forms the surface of the skin) • The second most common type of skin cancer. • Nonmelanoma skin cancer. • All SCC lesions are thought to begin via the repeated, uncontrolled division of cancer stem cells (CSC). 7 Basal Cell Carcinoma (皮膚基底細胞癌) • BCC arises in cells called basal keratinocytes in the deepest layer of the epidermis, hair follicles, and sweat ducts. • The most common type of skin cancer. • Nonmelanoma skin cancer. • Most BCCs occur on skin that is regularly exposed to sunlight or other ultraviolet radiation. • The only way to diagnose BCC is to biopsy suspicious looking lesions. 8 Melanocytes (黑色素細胞) • Melanocytes originate in the neural crest and migrate to the layer of basal cells at the deepest part of the epidermis and the hair matrices during embryogenesis. (Melanoblast) • A cell in the skin and eyes that produces and contains the pigment called melanin (黑色素). (Melanogenesis) 9 Melanoma (黑色素細胞癌) • Abnormal melanocytes are in the epidermis. These abnormal melanocytes may become cancer and spread into nearby normal tissue. • Melanoma is more aggressive than BCC or SCC. 10 Fibroblast (纖維母細胞) • The dermis is composed of three major types of cells: Fibroblasts, Macrophages, and Adipocytes. • Synthesizes the extracellular matrix and collagen. • Plays a critical role in wound healing. • Fibroblasts are the most common cells of connective tissue in animals. • The suffix "blast" is used in cellular biology to denote a stem cell or a cell in an activated state of metabolism. 11 Keratinocyte HaCaT • From the distant periphery of a melanoma located on the upper half of the back (not extensively sun-exposed) of a 62-yr-old male patient. • HaCaT is the first permanent epithelial cell line from adult human skin that exhibits normal differentiation and provides a promising tool for studying regulation of keratinization in human cells. – Maintains full epidermal differentiation capacity. • Named HaCaT to indicate the origin and initial growth conditions. Petra Boukamp et al. The Journal of Cell Biology, Volume of 106, March 1988 12 Squamous Cancer Cell A431 • The A431 cell line was derived from an 85-year-old female with epidermal carcinoma by D.J. Giard, et al. • One of the fastest growing malignant tumors • The cells carry large numbers of EGF binding sites and is an indicator cell for anti-TGF binding. 13 Basal Cell Carcinoma BCC-1/KMC • Derived from the undifferentiated type of facial BCC tumor on the thermal traumatic scar • This immortalized and tumorigenic cell line expresses epithelial markers of keratin filaments and desmosomes. Lien-Chai Chiang, et al. Kaohsiung J Med Sci 10: 170-176 1994 14 Melanoma A2058 • Established from a lymph node metastasis removed from a 43-yearold male Caucasian with malignant melanoma. • The cells are highly invasive and provide a source of cellular invasion associated proteins (such as the 72000 dalton type IV collagenase). 15 Melanoma A-375 • Derived from a 54-year-old female with malignant melanoma. • The line produced rapidly growing subcutaneous tumors resembling amelanotic melanomas in antithymocyte, serum-treated NIH Swiss mice and formed colonies on normal fibroblast and in agar. • Karyology: hypotriploid with a modal number of 62 chromosomes. 200X Image 16 Fibroblast Hs68 • The cell line was obtained from an apparently normal Caucasian newborn male. • This cell line has an unusually low level of the enzyme aspartoacylase. • Dr. Johnson pointed out that individuals exhibiting a deficiency in aspartoacylase suffer from Canavan disease (腦白質海綿狀變性). • Canavan disease is a devastating, autosomal recessive disorder involving spongy degeneration of the nervous system. 17 Summary Name Species Age Stage, Gender, Strain Ethnicity Organ Cell Type or Disease HaCaT Homo sapiens (human) 62 years, male, Caucasian Skin Keratinocyte; Periphery of a melanoma A-375 Homo sapiens (human) 54 years, female Skin Malignant melanoma A2058 Homo sapiens (human) 43 years, male, Caucasian Skin Melanoma; from metastatic site, lymph node A-431 Homo sapiens (human) 85 years, female Skin; Epidermis Epidermoid carcinoma Hs68 Homo sapiens (human) Newborn, male, Caucasian Skin; foreskin Fibroblast; aspartoacylase deficiency; possible Canavan disease BCC Homo sapiens (human) 65 years, female, Chinese Facial skin Nonmelanoma skin cancer; basal cell carcinoma M4 Melanoblast M5 Melanoblast 3T3 Mice Fibroblast 18 Reference • HaCaT – – • A2058 – – – – • – – – BCRC:https://www.bcrc.firdi.org.tw/BSAS_cart/controller?event=SEARCH&bcrc_no=60039&type_id=4&keyword=A;;3 75 ATCC:http://www.atcc.org/ATCCAdvancedCatalogSearch/ProductDetails/tabid/452/Default.aspx?ATCCNum=CRL1619&Template=cellBiology http://bioinformatics.istge.it/cldb/cl199.html http://bioinformatics.istge.it/cldb/cl198.html A-431 – – • BCRC: https://www.bcrc.firdi.org.tw/BSAS_cart/controller?event=SEARCH&bcrc_no=60240&type_id=4&keyword=A;;2058 ATCC: http://www.atcc.org/ATCCAdvancedCatalogSearch/ProductDetails/tabid/452/Default.aspx?ATCCNum=CRL11147&Template=cellBiology#aProp47ee8 http://bioinformatics.istge.it/cldb/cl190.html http://bioinformatics.istge.it/cldb/cl7207.html A-375 – • http://www.cell-lines-service.de/content/e143/e1779/e1298/index_ger.html normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line http://www.atcc.org/ATCCAdvancedCatalogSearch/ProductDetails/tabid/452/Default.aspx?ATCCNum=CRL1555&Template=cellBiology https://www.bcrc.firdi.org.tw/BSAS_cart/controller?event=SEARCH&bcrc_no=60161&type_id=4&keyword=A;;431 Hs68 – ATCC:http://www.atcc.org/ATCCAdvancedCatalogSearch/ProductDetails/tabid/452/Default.aspx?ATCCNum=CRL1635&Template=cellBiology 19