美阿尔贡国家实验室发现217种新抗癌靶子(2)

"We  wanted  to  find  the  proteins  that  are  only  made  when  the  endothelial  cells  are  making  a  capillary,  not  when  they  are  just  growing,"  Rodi  said.  "We  took  all  of  the  genes  that  were  made  on  the  tissue  plate  and  subtracted  out  those  from  the  plastic  plate.  And  we  were  left  with  217."

The  researchers  sought  the  proteins  in  the  capillaries  using  commercially  available  antibodies.  Of  the  16  morphogenesis-specific  proteins  tested,  all  were  found  in  the  capillaries  after  they  were  completely  formed.

The  capillary  research  revealed  a  bonus  insight  into  a  still  mysterious  nature  of  cells  –  their  polarity.  Cells  are  not  the  same  all  over  their  surface  –  different  sections  perform  different  tasks  like  acting  as  environmental  sensors  or  making  little  “feet”  to  mediate  cell  movement.  But  researchers  do  not  yet  know  all  of  the  genes  which  are  involved  in  polarity.

The  majority  of  the  217  proteins  identified  by  the  Argonne  group  manage  movement  within  the  cell,  long  distance  migration,  cytoskeletal  reorganization  and  cellular  stickiness  –  all  processes  involved  in  cell  polarity.  The  Argonne  study  revealed  that  more  angiogenic  genes  are  involved  in  polarity  than  previously  believed,  and  identified  a  large  number  of  novel  proteins  which  may  be  rate-limiting  for  the  angiogenic  process.

"This  information  will  help  with  developing  new  drugs,"  Rodi  said.  "Once  you  know  a  gene  product  helps  out  in  a  process,  then  it  automatically  becomes  a  possible  drug  target."

The  next  step  is  to  find  antibodies  to  the  rest  of  the  217  genes  –  only  about  50  are  commercially  available  –  and  determine  if  they  all  are  present  in  the  capillaries.  They  are  relying  on  a  novel  approach  to  express  human  proteins  high  throughput  in  bacteria  that  other  Argonne  biologists  are  in  the  process  of  developing.  Long-term  research  could  lead  to  new  medications  for  cancer  as  well  as  for  eczema,  macular  degeneration  and  rheumatoid  arthritis  –  other  diseases  involving  pathological  capillary  formation.   (责任编辑：泉水)

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美阿尔贡国家实验室发现217种新抗癌靶子(2)