대장직장암에서 CD105 (Endoglin)와 범내피세포 표지자 (CD34, CD31, Factor VIII) 발현에 의한 미세혈관밀도

김진수 외 중앙대학교 의과대학 의학연구소 2007 中央醫大誌 Vol.32 No.1/2

CD105 (endoglin) has been shown to be a more useful marker to identify proliferating endothelium involved in tumor angiogenesis than panendothelial markers such as CD34, CD31, and factor VIII. We investigated CD105 and panenthothelial markers expression as possible prognostic markers in colorectal cancer. Paraffin embedded tissue from 72 patients were immunostained for CD105, CD34, CD31, and Factor VIII. Positively stained microvessels were counted in densely vascular foci (hot spot) at ×200 field in each specimen. The microvessel density (MVD) by CD105 showed a statistically significant correlation with tumor emboli, T-stage, nodal metastasis, and stage. On MVD by panendothelial markers, a statistically significant correlation showed in tumor emboli and nodal metastasis in MVD by CD34, and histologic differentiation, tumor emboli, and nodal metastasis in MVD by Factor VIII. The MVD by CD105 may be correlated with invasiveness in colorectal cancer.

인체 무릎관절 윤활포식세포 cluster designation 표지에 관한 면역전자현미경적 연구

임형수,조국형,김용욱,박경한,황영일,장가용,황덕호,Lim, Hyoung-Soo,Cho, Kook-Hyeung,Kim, Yong-Wook,Park, Kyeong-Han,Hwang, Young-Il,Chang, Ka-Young,Hwang, Douk-Ho 한국현미경학회 2000 Applied microscopy Vol.30 No.2

사람 무릎관절 윤활막을 구성하는 윤활세포 중 윤활포식세포(phagocytic synovial cell, type A cell)의 기원에 대한 논의는 형태적으로 큰포식세포의 모습을 하고 있는 단핵포식체 계 (mononuclear phagocyte system)의 한 일부로서 아마도 골수(bone marrow)에서 기원되어졌을 것이라고 알려져 있다. 기능적으로도 LCA, HLA-DR과 Ia 항원에 양성반응을 보여 큰포식세포의 일부로 알려졌으나 아직 연구가 부족한 실정이다. 본 연구는 CD14와 활성화된 큰포식세포의 표지물로 알려진 CD105(endoglin)를 이용하여 윤활포식세포의 세포 내 발현부위를 규명하고, 기능적으로 활성화된 큰포식세포와 포식작용의 역할을 수행하는지 여부를 확인하기 위해 사람의 무릎관절에서 윤활세포들을 냉동초미세박절법을 이용한 면역조직화학 기법으로 CD14와 CB105에 대한 금표지를 하여 투과전자현미경으로 관찰한 결과 다음과 같은 결론을 얻었다. 1. CD14는 윤활포식세포의 과립세포질세망과 세포질및 가장자리, 공포 주변 부위에서 표지 되었으며 공포내에서는 표지 되지 많았다. 2. CD105(endoglin)는 윤활포식세포의 세포막 가장자리와 세포질 돌기를 따라 표지 되었으며 공포 주변 부위에서도 표지 되었으나, 공포 내에서는 표지 되지 많았다. 이상의 결과로 보아 사람 무릎관절 윤활세포층에 위치하는 윤활포식세포는 CD14와 CD105의 항원에 대한 표지를 보이므로 활성화된 큰포식세포나 포식작용의 역할을 수행하는 것으로 생각된다. This study was designed to observe the ultrastructural localization of synoviocytes, which are concerned with the function of phagocytic synovial cells (type A synoviocytes, macrophage-like synoviocytes), in the knee joint of the human for CD14 and CD105 by cryo-immune-electron microscopic technique. The synovium were dissected and fixed for two hours (in 4% paraformaldehyde and 0.1% glutaraldehyde mixture), and were immerged in 2.3 M sucrose and 20% PVP solution. Finally, they were cut with the cryoultramicrotome and labelled with primary antibodies (monoclonal mouse anti-human CD14, monoclonal mouse anti-human CD105 (endoglin) and secondary (donkey anti-mouse IgG) tagged with 6 nm colloidal gold particles. The tissues were observed under transmission electron microscope. This study was resulted as follows. 1. In the synovium of the human knee joint, CD14+ cells were identified. These cells showed phagocytic synovial cell's features. In the phagocytic synoviocyte, the distributions of CD14 were marked in the cytoplasm, around vacuoles, and in cytoplasmic process, but not detected inside of vacuoles. 2. In the synovium of the human knee joint, CD105+ cells were identified. These cells were recognized endothelial cells and phagocytic synovial cells. In the phagocytic synovial cells, the distributions of CD105 (endoglin) were marked in cytoplasic process, around vacuoles, and in cell membrane, but not detected inside of vacuoles. On the basis of above findings, it is obvious that phagocytic synovial cells were marked at CD 14 and CD 105, and might be play the role of activated macrophages or phagocytes in the synovial membrane.

Long Term Exposure to Myrtucommulone-A Changes CD105 Expression and Differentiation Potential of Mesenchymal Stem Cells

Kenan Izgi,Mehmet Fatih Sonmez,Halit Canatan,Banu Iskender 한국조직공학과 재생의학회 2017 조직공학과 재생의학 Vol.14 No.2

Mesenchymal stem cells (MSCs) represent a heterogeneous group of multipotent stem cells that could be found in various somatic tissues. MSCs are defined by molecular and functional features including spindle-shape morphology, adherence to plastic surfaces, expression of specific surface markers and differentiation potential to chondrocytes, adipocytes and osteocytes. The surface markers were proposed to affect the differentiation potential of MSCs by a limited number of studies. Endoglin (CD105) is defined to be a significant marker for osteogenic and chondrogenic differentiation ability of MSCs. Low CD105 expression is associated with increased osteogenic potential while high CD105 expression is correlated with strong chondrogenic potential. Myrtucommulone-A (MC-A) is an active compound with various biological effects on different cell types but its effect on MSC differentiation has not been described yet. In the present study we aimed at investigating the longterm effects of MC-A on hMSCs. MC-A-treatment reduced CD105 expression in distinct human mesenchymal stem cell (hMSC) lines and gave rise to CD105low population but did not change CD44, CD90 or CD73 expression. The decrease in CD105 expression reduced the chondrogenic potential of hMSCs subsequently while adipogenic or osteogenic differentiation was not affected dramatically. MC-A-treatment also suppressed the NF-jB p65 activation which might be responsible for the reduced chondrogenic potential. Our findings suggest thatMC-Acould be used to enrichCD105lowhMSCs without the need for cell sorting or changing culture conditions which could be utilised in targeted differentiation studies.

사람골수줄기세포가 연골조직으로 분화되는 과정에 나타나는 세포표지자의 표현

김상경 ( Sang Gyung Kim ),최정윤 ( Jung Yoon Choe ),김채기 ( Chae Gi Kim ),정승혜 ( Seung Hie Chung ),신임희 ( Im Hee Shin ),서헌석 ( Hun Suk Suh ) 대한류마티스학회 2005 대한류마티스학회지 Vol.12 No.1

Objective: Multipotent bone marrow stromal cells have the ability to differentiate toward a variety of connective tissue lineages including cartilage. The future use of adult mesenchymal stem cells (MSCs) for human therapies depends on the establishment of preclinical studies. Therefore, in this preclinical study we demonstrated the expression of MSC surface markers CD29, CD105, and CD44 on human bone marrow derived stromal cells during chondrogenic differentiation. Methods: Adult human bone marrow was collected from the iliac crest of 7 donors following informed consent. Mononuclear cells were isolated, incubated in monolayers, and embedded in alginate beads for three-dimensional cultures. Cellualr viability was assessed by MTT assay. Flow cytometry of alginate bead cultures was performed on days 0, 7, 14, 21, and 28 using monoclonal antibody against surface molecules, CD105, CD29, CD44, CD34 and CD45. Total contents of collagen and glycosaminoglycan (GAG) of the alginate beads was measured. SPSS 11.0 was used for data analysis. Results: After 7 days of culture, 89% of the cells expressed the human integrin beta 1 antibody, CD29. The CD29-positive cells remained elevated at 83% on days 28. However, while only 18% expressed the type II TGF-beta receptor endoglin, CD105 on day 7, the CD105-positive cells increased abruptly 65% on day 14 remaining elevated up to day 28. The expression of CD44 was maximal in the first passage cell (63%). High concentration of TGF-beta 3 (10 ng/mL) was more favorable for sustaining cell viability than a low concentration (0.5 ng/mL)(n=4, p=0.002, day 21). The total contents of collagen and GAG in the MSC-alginate beads increased during the three-dimensional culture (n=4, p=0.02, p=0.006) suggesting its differentiation into a chondrogenic lineage. Conclusion: CD29 was expressed earlier than CD105 during chondrogenic differentiation of human bone marrow MSC. CD44 expression was highest in the first passage cells and gradually decreased afterwards.

위암의 내시경하 생검 조직에서 CD105 (Endoglin), D2- 40, Vasc ular Endothelial Growth Fac tor- A와 D의 발현을 통한 침습성의 예측

김성수(Sungsoo Kim),이태진(Tae Jin Lee),김범규(Beom Kyu Kim),차성재(Sung Jae Cha),박성준(Sung Jun Park),장인택(In Taek Chang),박성일(Sung Il Park) 대한외과학회 2007 Annals of Surgical Treatment and Research(ASRT) Vol.72 No.5

Purpose: CD105 (endoglin) has been shown to be a more useful marker to identify the proliferating endothelium involved in tumor angiogenesis than are the panendothelial markers. The monoclonal antibody D2-40 is a specific lymphatic endothelial marker. Methods: We investigated CD105, lymphatic vessel marker (D2-40), vascular endothelial growth factor (VEGD)-A and the VEGF-D expressions as possible prognostic markers in the endoscopic biopsy tissue of stomach cancer patients. The pre-operative endoscopic biopsies and surgical biopsies from 73 patients were immunostained for CD105, D2-40, VEGF-A and VEGF-D. Positively stained microvessels were counted in densely vascular foci (hot spots) at a ×200 field in each specimen. Results: The microvessel density (MVD) and lymphatic vessel density (LVD), according to the CD105 and D2-40 expressions of the endoscopic biopsies, showed a statistically significant correlation with the surgical biopsies. The MVD via CD105 a showed statistically significant correlation with the histologic differentiation, T-stage, nodal metastasis and stage in the endoscopic biopsies and surgical biopsies, respectively. The lympathic vessel density (LVD) via D2-40 showed a statistically significant correlation with T-stage, nodal metastasis and stage in the endoscopic biopsies. The expressions of VEGF-A and VEGF-D showed a statistically significant correlation with the MVD and LVD. Conclusion: The MVD, as determined by the CD105 expression and the LVD as determined by the D2-40 expression may be useful markers for predicting the invasiveness with using a pre-operative endoscopic biopsy of stomach cancer.

대장직장암에서 수술 전 생검 조직의 범내피세포와 림프관 표지자 발현의 의의

한규성(Gue Sung Han),김범규(Beom Gyu Kim),차성재(Seong Jae Cha),장인택(In Taek Chang),이태진(Tae Jin Lee) 대한외과학회 2007 Annals of Surgical Treatment and Research(ASRT) Vol.73 No.2

Purpose: Panendothelial markers such as factor Ⅷ, CD34, CD31, CD105 (endoglin) and D2-40 are useful to identify proliferating endothelium that is related to tumor invasion. This study was designed to identify the correlation between the expressions of panendothelial and lymphatic vessel markers in preoperative biopsy specimens and the clinicopathologic factors. Methods: Preoperative biopsy specimens from 72 patients were immunostained for CD105, CD34, CD31, Factor Ⅷ and D2-40. The microvessel and lympathic vessel densities (MVD and LVD) were counted in dense vascular foci (hot spots) on a ×200 field in each specimen. The correlation between these factors and the clinicopathologic parameters were analyzed. Results: The MVD by CD105 showed statistically significant correlation with tumor emboli, the T-stage, nodal metastasis and the stage, and the MVD by CD34 had statistically significant correlation with tumor emboli, nodal metastasis and the stage. The lympathic vessel density (LVD) by D2-40 showed a statistically significant correlation with tumor emboli, the T-stage and nodal metastasis. Conclusion: The MVD by CD105 and the LVD by D2-40 in preoperative biopsy specimens of colorectal cancers may be useful markers for the prediction of invasiveness.

Expression of Ki67 and CD105 as Proliferation and Angiogenesis Markers in Salivary Gland Tumors

Tadbir, Azadeh Andisheh,Pardis, Soheil,Ashkavandi, Zohreh Jafari,Najvani, Ali Dehghani,Ashraf, Mohammad Javad,Taheri, Ali,Zadeh, Maryam Asad,Sardari, Yasaman Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.10

Objective: To investigate the association between CD105 and tumor cell proliferation in salivary gland tumors. Methods: In this study, 59 samples of salivary tumors from Khalili Hospital archive, including 20 cases of pleomorphic adenoma (PA), 20 cases of mucoepidermoid carcinoma (MEC) and 19 cases of adenoid cystic carcinoma, as well as 10 cases of normal salivary gland tissue, were reviewed by immunohistochemistry (IHC) for CD105 and Ki67 staining. Results: CD105 positive vessels were absent in normal salivary gland tissue in the vicinity of tumors (51.6% of all tumors were positive). There was a statistically significant difference in frequency of CD105 staining between PA and malignant tumors and between four groups of different lesions (p<0.000) being highest in MEC. Intratumoral microvessel density was also elevated in malignant neoplasms ($2.61{\pm}3.1$) as compared to PA ($0.46{\pm}0.6$). Normal salivary glands did not express Ki67. There was a statistically significant difference in frequency and percentage of Ki67 immunoreactivity in malignant neoplasms (86.5% and $10.7{\pm}10.8$ respectively) compared to PA (50% and $0.78{\pm}0.2$) and among the four groups values were highest in MEC (p<0.000). Conclusion: n this study, it was observed a higher rate of angiogenesis and cellular proliferation was noted in malignant tumors compared to benign tumors, but no correlation was observed between these two markers.

Annexin A2 and CD105 Expression in Pancreatic Ductal Adenocarcinoma is Associated with Tumor Recurrence and Prognosis

Huang, Ya-Kai,Liu, Hong,Wang, Xin-Zheng,Zhu, Shan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.22

To investigate the value of expression of annexin A2, microvessel density (MVD) and CD105 in pancreatic ductal adenocarcinoma (PDAC) tissues and adjacent normal tissues, immunohistochemical staining was used. The positive expression rate of Annexin A2 and the MVD in pancreatic ductal adenocarcinoma tissues was higher than that in in adjacent normal tissues (p<0.005). Expression of Annexin A2 and MVD correlated with histological grade (p<0.05). MVD of cancers in TNM stage IIb was higher than that in TNM stageI~IIa (p<0.026). Cancerous tissues with Annexin A2 staining grade 3+ had lower MVD than the tissues with the other Annexin A2 staining grade (p<0.05). Patients with high MVD had worse prognosis. However, our study did not confirm Annexin A2 was an independent risk factor for patients with PDAC. We confirmed MVD labeled by CD105 was an independent risk factor for patients with PDAC and had moderate predictive value of prognosis.