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피부암에서 ADAM-family protease의 발현과 기능
이 보고서는 한국연구재단(NRF, National Research Foundation of Korea)이 지원한 연구과제( 피부암에서 ADAM-family protease의 발현과 기능 | 2007 년 신청요강 다운로드 PDF다운로드 | 오신택(가톨릭대학교& #40;성의교정& #41;) ) 연구결과물 로 제출된 자료입니다.
한국연구재단 인문사회연구지원사업을 통해 연구비를 지원받은 연구자는 연구기간 종료 후 6개월 이내에 결과보고서를 제출하여야 합니다.(*사업유형에 따라 결과보고서 제출 시기가 다를 수 있음.)
  • 연구자가 한국연구재단 연구지원시스템에 직접 입력한 정보입니다.
연구과제번호 E00045
선정년도 2007 년
과제진행현황 종료
제출상태 재단승인
등록완료일 2008년 08월 26일
연차구분 결과보고
결과보고년도 2008년
결과보고시 연구요약문
  • 국문
  • 1. The disintegrin-metalloproteinases ADAM 10, ADAM 12 and ADAM 17 are upregulated in invading peripheral tumor cells of basal cell carcinomas : 피부 기저세포암에서 면역조직학적 방법을 이용하여 연구한 결과 ADAM 10,12,17이 종양의 침습부위에서 증가함을 관찰하였고 특히 ADAM10, 12는 혼합형아형에서 증가함을, 그리고 ADAM12는 편평상피세포화된 아형에서 증가하여 종양의 분화와 관련이 있음을 알 수 있었고, ADAM17은 표재형아형에서 증가하여 즉 ADAM17이 초기 기저세포암의 발생에 관련이 있음을 알 수 있었다.
    2. Immunohistochemical analysis of ADAM 10, 12 in normal and psoriatic skin
    : 파라핀화된 건선피부조직에서 면역조직학적 방법을 이용하여 연구한 결과 ADAM ADAM 10, 12가 정상 조직에 비해 건선피부에서 증가함을 관찰할 수 있었다.
    3. Overexpression of CXCL16 in lesional psoriatic skin
    : 파라핀화된 건선피부조직에서 면역조직학적 방법을 이용하여 연구한 결과 CXCL16이 정상 조직에서는 상부표피에 발현하여 virus나 bacteria에 대한 barrie역할을 하리라 생각되며 건선에서는 하부표피에서 발현이 매우 증가하여 아마도 T lymphocyte의 recruitment에 관여하리라 생각되며, 또한 진피내 혈관에 발현이 증가하여 혈관내에서 leukocyte의 diapedesis에 관여하며 T lymphocyte의 recruitment에 에도 또한 관여하리라 생각된다.
  • 영문
  • 1. The disintegrin-metalloproteinases ADAM 10, ADAM 12 and ADAM 17 are upregulated in invading peripheral tumor cells of basal cell carcinomas : we detected that expression of ADAM 10, 12, 17 was increased in the deep invasion area of peripheral BCC tumor cells, indicating that these three proteases may play an important role in the locally invasive and highly destructive growth behaviour of BCC tumor cells. Overexpression of ADAM 17 in superficial BCC indicates that ADAM 17 may play an important role in the development of BCC. Increased ADAM 12 immunoreactivity was found in the foci of nodular BCC with squamous differentiation, indicating that ADAM12 may play an important role in BCC with squamous differentiation. Therefore, we suggest that ADAM 10, 12, 17 showed different expression pattern in BCC histologic subtypes, indicating their different role in the BCC pathogenesis. In addition, inhibitors of ADAM 10, 12, 17 may be useful as a novel therapeutic modality.

    2. Immunohistochemical analysis of ADAM 10, 12 in normal and psoriatic skin
    : ADAM 10 and ADAM 12 may be of importance for key events of the developing psoriatic lesion, including leukocyte recruitment and migration, exocytosis of neutrophils in epidermal cell layers and alterations in keratinocytes proliferation/differentiation. In future, the functional role of both metalloproteinases in psoriasis have to be investigated in more detail to evaluate the importance of ADAM 10 and ADAM 12 in this disease.

    3. Overexpression of CXCL16 in lesional psoriatic skin
    : the major findings of the present study were as follows: 1) expression of CXCL16 is abundant in lower psoriatic epidermal keratinocytes, 2) expression of CXCL16 is increased in all capillary endothelial cells in the psoriatic dermis. These results indicate that CXCL16 may be of importance for the pathogenesis of psoriasis, involving leukocyte recruitment and migration, and alterations in keratinocytes proliferation/differentiation. Therefore, further studies should be performed to investigate if CXCL16 could be a potentially useful therapeutic target for the treatment of psoriasis patients.
연구결과보고서
  • 초록
  • 1. The disintegrin-metalloproteinases ADAM 10, ADAM 12 and ADAM 17 are upregulated in invading peripheral tumor cells of basal cell carcinomas.

    Background: Members of the ADAM family are expressed in malignant tumours and participate in the pathogenesis of cancer. However, the presence of ADAM 10, 12, 17 and their role in basal cell carcinoma (BCC) have not been described. The purpose of this study was to investigate ADAM 10, 12 and 17 expression in BCC.
    Methods: ADAM 10, 12, 17 expression was analyzed by immunohistochemistry in skin tissues obtained from 25 patients with different types of BCC.
    Results: ADAM 10, 12, 17 immunoreactivity was increased at the peripheral tumor margin as compared to central areas of BCC tumor cell nests. Immunoreactivity of ADAM 10, 12 was increased in the deep margin of invading tumor cell nests in mixed BCC. Exceptionally immunoreactivity of ADAM 17 was increased in superficial BCC. In addition, focally increased expression of ADAM 12 was detected in squamoid differentiated tumor cells of nodular BCC.
    Conclusions: ADAM 10, 12, 17 showed different expression pattern in BCC histologic subtypes, indicating their different role in the BCC pathogenesis. Overexpression of ADAM 10, 12, 17 immunoreactivity in deep invasion area of BCC, indicates that these three proteases may play an important role in the locally invasive and highly destructive growth behaviour of BCC. Additionally, we suggest that ADAM 17 may play an important role in early development of BCC. These results imply that inhibitors of ADAM 10, 12, 17 may be useful as a novel therapeutic modality.

    2. Overexpression of CXCL16 in lesional psoriatic skin

    Background: Psoriasis is characterized as an autoimmune disease resulting in an exaggerated innate immune response. The CXC-chemokine ligand 16 (CXCL16) is described to function as an adhesion molecule, a scavenger receptor or as a soluble molecule it acts as a chemoattractant. CXCL16 has been reported to be expressed in a variety of inflammatory diseases. However, no information has been reported in the literature about the expression of CXCL16 in psoriatic skin.
    Purpose: The present study was designed to analyze the expression and localization of CXCL16 in human psoriatic skin tissues.
    Materials and methods: 10 paraffinized specimens of human lesional psoriatic skin and 5 paraffinized specimens of normal skin were studied using an immunohistochemical streptavidin-peroxidase technique.
    Results: In normal skin, cytpoplasmic expression of CXCL16 was increased in keratinocytes of upper epidermal cell layers as compared to the lower epidermal cell layers. In lesional psoriatic skin, CXCL16 immunoreactivity was increased in the cytoplasm of keratinocytes of lower epidermal layer kerartinocytes as compared to the normal epidermis. Cytoplasmic CXCL16 expression was increased in the capillary endothelial cells of psoriatic dermis as compared to capillary endothelial cells of the normal dermis. Notably, almost all inflammatory cells in the dermis were negative for CXCL16.
    Conclusion: We here report for the first time alterations in the immunohistochemical staining pattern of CXCL16 in lesional psoriatic skin compared to the normal skin. These results suggest that CXCL16 may play a role in the pathogenesis of psoriasis.
  • 연구결과 및 활용방안
  • 1. The disintegrin-metalloproteinases ADAM 10, ADAM 12 and ADAM 17 are upregulated in invading peripheral tumor cells of basal cell carcinomas : ADAM 10,12,17이 종양의 침습부위에서 증가함을 관찰하였고 특히 ADAM10, 12은는 혼합형아형에서 증가함을 , 그리고 ADAM12는 편평상피세포화된 아형에서 증가하였으며, ADAM17 표재형아형 즉 초기 기저세포암의 발생에 관련이 있음을 알 수 있었다. 따라서 ADAM protease가 기저세포암의 발생과 관련이 있으며, 종양의 분화 및 종양의 침습과 관련이 있어 기저세포암의 치료제의 개발에 도움이 될 수 있으리라 생각된다.
    2. Immunohistochemical analysis of ADAM 10, 12 in normal and psoriatic skin
    : ADAM 10, 12가 정상 조직에 비해 건선피부에서 증가하여 건선의 발생에 관여하며 새로운 치료제의 개발에 도움이 되리라 생각된다 .
    3. Overexpression of CXCL16 in lesional psoriatic skin
    : CXCL16이 정상 조직에서는 상부표피에 발현하여 virus나 bacteria에 대한 barrie역할을 하리라 생각되며 건선에서는 하부표피에서 발현이 매우 증가하여 아마도 T lymphocyte의 recruitment에 관여하리라 생각되며, 또한 진피내 혈관에 발현이 증가하여 혈관내에서 leukocyte의 diapedesis에 관여하며 T lymphocyte의 recruitment에 에도 또한 관여하리라 생각된다. 또한 건선에서 표피나 진피혈관의 증식에도 관여하리라 생각되며 이를 치료에 응용할 수도 있으리라 생각된다.
  • 색인어
  • Basal cell carcinoma, ADAM 10, ADAM 12, ADAM 17
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