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April 28, 2009

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Cancer cells may “prepare” earlier than thought 

Aug. 29, 2008
Courtesy Science
and World Science staff

The spread of can­cer to new sites in the bod­y—the pro­cess ul­ti­mately re­spon­si­ble for most can­cer deaths—may hap­pen ear­li­er in the dis­ease pro­cess than was pre­vi­ously thought, new re­search on mice sug­gests. 

Sci­en­tists said the find­ing sug­gests an ex­plana­t­ion for why some breast can­cers, for ex­am­ple, me­tas­ta­size, or spread, long af­ter the in­i­tial tu­mor has been treated. 

Be­cause can­cer me­tas­ta­sis in­volves many step­s—the cells must be equipped to sur­vive a trip in the blood­stream and start ma­lig­nant growth in a new ar­ea of the bod­y—re­search­ers have tra­di­tion­ally con­sid­ered it to be a late event in can­cer pro­gres­sion. Ac­cord­ing to this view, me­tas­ta­sis oc­curs af­ter pri­ma­ry tu­mor cells have racked up a se­ries of ge­net­ic al­tera­t­ions that switch on can­cer genes. 

The new re­sults, scientists said, sug­gest met­a­stat­ic dis­ease might in­stead arise from nor­mal cells that spread early in the dis­ease. These re­main dor­mant at the new or­gan site un­til can­cer genes are switched on.

In the stu­dy, Ka­tri­na Pod­sy­pan­ina at Me­mo­ri­al Sloan-Kettering Can­cer Cen­ter in New York and col­leagues in­jected mice with mam­ma­ry cells ma­ni­pu­lated in a way that al­lowed re­search­ers to turn on cer­tain can­cer genes, or “on­co­ge­nes,” at var­i­ous times af­ter in­jec­tion. 

The re­search­ers found that the nor­mal mam­ma­ry cells could trav­el in the blood­stream to the lungs and sur­vive there up to four months with­out ac­ti­vat­ing any on­co­genes. The cells did­n’t beg­in grow­ing ag­gres­sively un­til the onc­o­genes had been turned on.

Ex­am­in­ing each step of the pro­cess by which can­cer me­tas­ta­sizes, in­clud­ing those in­volv­ing nor­mal cells, might al­low sci­en­tists to iden­ti­fy new stra­te­gies for de­stroy­ing the cells re­spon­si­ble for the spread, ac­cord­ing to Pod­sy­pan­ina and col­leagues. The find­ings ap­pear in the Aug. 29 is­sue of the re­search jour­nal Sci­ence.

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The spread of cancer to new sites in the body—the process that is ultimately responsible for most cancer deaths—may happen earlier in the disease process than was previously thought, new research on mice suggests. Scientists said the finding suggests an explanation for why some breast cancers, for example, metastasize, or spread, long after the initial tumor has been treated. Because cancer metastasis involves many steps—the cells must be equipped to survive a trip in the bloodstream and start malignant growth in a new area of the body—researchers have traditionally considered it to be a late event in cancer progression. According to this view, metastasis occurs after primary tumor cells have racked up a series of genetic alterations that switch on cancer genes. The new results suggest metastatic disease might instead arise from normal cells that spread early in the disease and remain dormant at the new organ site until cancer genes are switched on. In the study, Katrina Podsypanina at Memorial Sloan-Kettering Cancer Center in New York and colleagues injected mice with mammary cells manipulated in a way that allowed researchers to turn on certain cancer genes, or “oncogenes,” at various times after injection. The researchers found that the normal mammary cells were capable of traveling in the bloodstream to the lungs and surviving there for up to four months without activating any oncogenes. These cells didn’t begin growing aggressively until the oncogenes had been turned on. Examining each step of the process by which cancer metastasizes, including those involving normal cells, might allow scientists to identify new strategies for destroying the cells responsible for the disease’s spread through the body, according to Podsypanina and colleagues. The findings appear in the Aug. 29 issue of the research journal Science.