title: Diminished metastasis in tetraspanin CD151-knockout mice.
abstract: Tetraspanin protein CD151 on tumor cells supports invasion and metastasis. In the present study, we show that host animal CD151 also plays a critical role. CD151-null mice showed markedly diminished experimental lung metastasis after injection of Lewis lung carcinoma or B16F10 melanoma cells. Diminished tumor cell residence in the lungs was evident 6-24 hours after injection. Consistent with an endothelial cell deficiency, isolated CD151-null mouse lung endothelial cells showed diminished support for B16F10 adhesion and transendothelial migration, diminished B16F10-induced permeability, and diminished B16F10 adhesion to extracellular matrix deposited by CD151-null mouse lung endothelial cells. However, CD151 deletion did not affect the size of metastatic foci or subcutaneous primary B16F10 tumors, tumor aggregation, tumor clearance from the blood, or tumor-induced immune cell activation and recruitment. Therefore, the effects of host CD151 on metastasis do not involve altered local tumor growth or immune surveillance. VEGF-induced endothelial cell signaling through Src and Akt was diminished in CD151-null endothelial cells. However, deficient signaling was not accompanied by reduced endothelial permeability either in vitro (monolayer permeability assay) or in vivo (VEGF-stimulated Miles assay). In summary, diminished metastasis in CD151-null host animals may be due to impaired tumor-endothelial interactions, with underlying defects in mouse lung endothelial cell extracellular matrix production.
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA 02215-5450, USA.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Takeda
authors.forename: Qinglin
authors.initials: Q
authors.lastname: Li
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Kazarov
authors.forename: Mathieu
authors.initials: M
authors.lastname: Epardaud
authors.forename: Kutlu
authors.initials: K
authors.lastname: Elpek
authors.forename: Shannon J
authors.initials: SJ
authors.lastname: Turley
authors.forename: Martin E
authors.initials: ME
authors.lastname: Hemler
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000502:physiology; D018827:Carcinoma, Lewis Lung / Q000235:genetics / Q000473:pathology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics / Q000502:physiology; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D008175:Lung Neoplasms / Q000235:genetics / Q000556:secondary; D008546:Melanoma, Experimental / Q000235:genetics / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009362:Neoplasm Metastasis / Q000235:genetics*; D009368:Neoplasm Transplantation; D060185:Tetraspanin 24; D057688:Transcellular Cell Migration / Q000235:genetics; D057705:Transendothelial and Transepithelial Migration / Q000235:genetics
chemical_list: D015703:Antigens, CD; C554716:Cd151 protein, mouse; D060185:Tetraspanin 24