目的观测黏附分子CD49b和负性调节分子淋巴细胞活化基因3(LAG-3)在反复自发性流产(RSA)患者CD14+细胞上的表达。方法收集7例正常对照者和12例RSA患者外周血5 m L,分离外周血单个核细胞(PBMC)和血浆,流式细胞术检测PBMC中CD14+细胞表面CD...目的观测黏附分子CD49b和负性调节分子淋巴细胞活化基因3(LAG-3)在反复自发性流产(RSA)患者CD14+细胞上的表达。方法收集7例正常对照者和12例RSA患者外周血5 m L,分离外周血单个核细胞(PBMC)和血浆,流式细胞术检测PBMC中CD14+细胞表面CD49b和LAG-3的表达;ELISA检测血浆中细胞因子白细胞介素10(IL-10)和转化生长因子β(TGF-β)的水平。结果 RSA患者外周血中,单核细胞的比例与正常对照组相比无显著性差异;CD14+CD49b+、CD14+LAG-3+、CD14+CD49b+LAG-3+细胞的百分比均低于正常对照组。血浆中,TGF-β的水平低于正常对照组;IL-10的水平无显著差异。结论 RSA患者外周血CD14+细胞表面CD49b和LAG-3的表达和血浆中TGF-β的水平均显著降低。展开更多
Integrins are cell adhesion molecules that are composed of an alpha(a)subunit and a beta(b)subunit with affinity for different extracellular membrane components.The integrin family includes 24 known members that activ...Integrins are cell adhesion molecules that are composed of an alpha(a)subunit and a beta(b)subunit with affinity for different extracellular membrane components.The integrin family includes 24 known members that actively regulate cellular growth,differentiation,and apoptosis.Each integrin heterodimer has a particular function in defined contexts as well as some partially overlapping features with other members in the family.As many reviews have covered the general integrin family in molecular and cellular studies in life science,this review will focus on the specific regulation,function,and signaling of integrin a2 subunit(CD49b,VLA-2;encoded by the gene ITGA2)in partnership with b1(CD29)subunit in normal and cancer cells.Its roles in cell adhesion,cell motility,angiogenesis,stemness,and immune/blood cell regulations are discussed.The pivotal role of integrin a2 in many diseases such as cancer suggests its potential to be used as a novel therapeutic target.展开更多
Cancer metastasis is largely incurable and accounts for 90%of breast cancer deaths,especially for the aggressive basal-like or triple negative breast cancer(TNBC).Combining patient database analyses and functional stu...Cancer metastasis is largely incurable and accounts for 90%of breast cancer deaths,especially for the aggressive basal-like or triple negative breast cancer(TNBC).Combining patient database analyses and functional studies,we examined the association of integrin family members with clinical outcomes as well as their connection with previously identified microRNA regulators of metastasis,such as miR-206 that inhibits stemness and metastasis of TNBC.Here we report that the integrin receptor CD49b-encoding ITGA2,a direct target of miR-206,promotes breast cancer stemness and metastasis.ITGA2 knockdown sup-pressed self-renewal related mammosphere formation and pluripotency marker expression,in-hibited cell cycling,compromised migration and invasion,and therefore decreased lung metastasis of breast cancer.ITGA2 overexpression reversed miR-206-caused cell cycle arrest in G1.RNA sequencing analyses revealed that ITGA2 knockdown inhibits genes related to cell cycle regulation and lipid metabolism,including CCND1 and ACLY as representative targets,respectively.Knockdown of CCND1 or ACLY inhibits mammosphere formation of breast cancer cells.Overexpression of CCND1 rescues the phenotype of ITGA2 knockdown-induced cell cycle arrest.ACLY-encoded ATP citrate lyase is essential to maintain cellular acetyl-CoA levels.CCND1 knockdown further mimics 1TGA2 knodkdown in abolishing lung colonization of breast cancer cells.We identified that the low levels of miR-206 as well as high expression levels of 1TGA2,ACLY and CCND1 are associated with an unf avor able relapse-free survival of the pa-tients with estrogen receptor-negative or high grade breast cancer,especially basal-like or TNBC,possibly serving as potential biomarkers of cancer stemness and thera peutic targets of breast cancer metastasis.展开更多
文摘目的观测黏附分子CD49b和负性调节分子淋巴细胞活化基因3(LAG-3)在反复自发性流产(RSA)患者CD14+细胞上的表达。方法收集7例正常对照者和12例RSA患者外周血5 m L,分离外周血单个核细胞(PBMC)和血浆,流式细胞术检测PBMC中CD14+细胞表面CD49b和LAG-3的表达;ELISA检测血浆中细胞因子白细胞介素10(IL-10)和转化生长因子β(TGF-β)的水平。结果 RSA患者外周血中,单核细胞的比例与正常对照组相比无显著性差异;CD14+CD49b+、CD14+LAG-3+、CD14+CD49b+LAG-3+细胞的百分比均低于正常对照组。血浆中,TGF-β的水平低于正常对照组;IL-10的水平无显著差异。结论 RSA患者外周血CD14+细胞表面CD49b和LAG-3的表达和血浆中TGF-β的水平均显著降低。
基金This manuscript is partially supported by the funds from the National Institutes of Health/National Cancer Institute(NIH/NCI)R00CA160638(H.L.)its Supplement for Diversity(V.A.),American Cancer Society 127951-RSG-15-025-01-CSM(H.L.)+1 种基金Susan G.Komen Foundation CCR15332826(H.L.)Department of Defense W81XWH-16-1-0021(H.L.).
文摘Integrins are cell adhesion molecules that are composed of an alpha(a)subunit and a beta(b)subunit with affinity for different extracellular membrane components.The integrin family includes 24 known members that actively regulate cellular growth,differentiation,and apoptosis.Each integrin heterodimer has a particular function in defined contexts as well as some partially overlapping features with other members in the family.As many reviews have covered the general integrin family in molecular and cellular studies in life science,this review will focus on the specific regulation,function,and signaling of integrin a2 subunit(CD49b,VLA-2;encoded by the gene ITGA2)in partnership with b1(CD29)subunit in normal and cancer cells.Its roles in cell adhesion,cell motility,angiogenesis,stemness,and immune/blood cell regulations are discussed.The pivotal role of integrin a2 in many diseases such as cancer suggests its potential to be used as a novel therapeutic target.
基金This manuscript has been partially supported by NIH/NCI grants R00CA160638 and R01CA245699(H.L.),and Supple-ment for Diversity(V.A.),T32 CA080621-15(R.T.),and R01CA213843(R.A.K),American Cancer Society grant ACS127951-RSG-15-025-01-CSM(H.L.)the Susan G.Komen Foundation CCR15332826(H.L.)and CCR18548501(X.L.)+3 种基金the Department of Defense W81XWH-16-1-0021(H.L.)the Lynn Sage Cancer Research Foundation(X.L.and H.L.)North-western University’s Endocrinology Training Grant T32DK007169-39(A.H.)and start-up funds fromCaseWestern Reserve University and at Northwestern University(H.L.).
文摘Cancer metastasis is largely incurable and accounts for 90%of breast cancer deaths,especially for the aggressive basal-like or triple negative breast cancer(TNBC).Combining patient database analyses and functional studies,we examined the association of integrin family members with clinical outcomes as well as their connection with previously identified microRNA regulators of metastasis,such as miR-206 that inhibits stemness and metastasis of TNBC.Here we report that the integrin receptor CD49b-encoding ITGA2,a direct target of miR-206,promotes breast cancer stemness and metastasis.ITGA2 knockdown sup-pressed self-renewal related mammosphere formation and pluripotency marker expression,in-hibited cell cycling,compromised migration and invasion,and therefore decreased lung metastasis of breast cancer.ITGA2 overexpression reversed miR-206-caused cell cycle arrest in G1.RNA sequencing analyses revealed that ITGA2 knockdown inhibits genes related to cell cycle regulation and lipid metabolism,including CCND1 and ACLY as representative targets,respectively.Knockdown of CCND1 or ACLY inhibits mammosphere formation of breast cancer cells.Overexpression of CCND1 rescues the phenotype of ITGA2 knockdown-induced cell cycle arrest.ACLY-encoded ATP citrate lyase is essential to maintain cellular acetyl-CoA levels.CCND1 knockdown further mimics 1TGA2 knodkdown in abolishing lung colonization of breast cancer cells.We identified that the low levels of miR-206 as well as high expression levels of 1TGA2,ACLY and CCND1 are associated with an unf avor able relapse-free survival of the pa-tients with estrogen receptor-negative or high grade breast cancer,especially basal-like or TNBC,possibly serving as potential biomarkers of cancer stemness and thera peutic targets of breast cancer metastasis.
