title: CD41 and CD45 expression marks the angioformative initiation of neovascularisation in human haemangioblastoma.
abstract: The initiation and formation of haemangioblastoma (HB) neovascularisation remain unknown, with concomitant controversy on its cytological origin. We detected HB-derived specific haematopoietic progenitors identified by surface expression of CD41 and CD45, which are similar to human embryonic vasculogenesis. CD41/CD45 cells expressed mesodermal markers, including SCL, Flk1 and c-kit. CD41 also seemed to appear before CD45 on haematopoietic progenitors. In vitro analysis showed that the CD41(+)/CD45 subpopulation gave rise to occasional primitive erythroid activity and endothelial marker expression. Meanwhile, kinetic investigation of the CD41(+)/CD45(+) subpopulation showed that some molecules, including SCL, Flk1 and c-kit, were involved in vascular formation. The CD45(+)/c-kit(+) population that lacked primitive haematopoiesis came from CD41(+) cells. Acquisition of CD45 expression by the haematopoietic progenitors was associated with advanced differentiation towards the vascular cell lineage. Taken together, the present data suggested that CD41 and CD45 expression marked the onset of HB neovascularisation and the stepwise development of the angioformative period. Our findings provide new insights into the mechanisms of HB neovascularisation and the underlying therapeutic targets of anti-vascular treatment.
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Wulumuqi Road 12#, Shanghai, 200040, China.
authors.forename: Dexuan
authors.initials: D
authors.lastname: Ma
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Wulumuqi Road 12#, Shanghai, 200040, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Wulumuqi Road 12#, Shanghai, 200040, China.
authors.forename: Guhong
authors.initials: G
authors.lastname: Du
authors.affiliation: Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.|Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
authors.forename: Jingyun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Wulumuqi Road 12#, Shanghai, 200040, China.
authors.forename: Qisheng
authors.initials: Q
authors.lastname: Tang
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Wulumuqi Road 12#, Shanghai, 200040, China. lfzhouc@126.com.
authors.forename: Liangfu
authors.initials: L
authors.lastname: Zhou
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D045744:Cell Line, Tumor; D002528:Cerebellar Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018325:Hemangioblastoma / Q000098:blood supply / Q000235:genetics / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000378:metabolism*; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism*; D040201:Platelet Membrane Glycoprotein IIb / Q000235:genetics / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D040201:Platelet Membrane Glycoprotein IIb; D019009:Proto-Oncogene Proteins c-kit; D017493:Leukocyte Common Antigens
keywords: Angiogenesis; Haemangioblastomas; Molecular characterization; Neovascularisation; Vasculogenesis