Phambi kwamathumba e-pancreatic, iiseli ezithile zokhuselo lomzimba ziqhekeza iiproteni zesakhiwo kwiimolekyuli ezibangela ukwakhiwa kwezicubu ezixineneyo, umqobo owaziwayo kunyango, uphando olutsha lufumanisa.
Ikhokelwa ngabaphandi abavela kwi-NYU Grossman School of Medicine, uphononongo lujikeleza kwiprotein exineneyo ye-meshwork exhasa amalungu kwaye inceda ekwakheni kwakhona izicubu ezonakalisiweyo. I-collagen protein fibers, eyona nto iphambili ye-mesh, ihlala ichithwa kwaye ithathelwa indawo ukuze kugcinwe amandla okuqina, kwaye njengenxalenye yenkqubo yokuphilisa inxeba.
Uphononongo oludlulileyo lubonise ukuba iiseli zokhuselo lomzimba ezibizwa ngokuba zii-macrophages zinegalelo kwinkqubo ebizwa ngokuba yi-desmoplasia, ebangelwa yinguqu engaqhelekanga kunye nokubekwa ngokugqithisileyo kwe-collagen ekhusela umhlaza wepancreatic. Kule meko, i-macrophages iyaziwa ngokuba yi-engulf kwaye iphule i-collagen ngesenzo seprotheni ebizwa ngokuba yi-mannose receptor (MRC1).
Ukupapasha i-intanethi ye-4 ka-Aprili kwiiNkcukacha zeSizwe zeSayensi zeSayensi, uphando lwangoku lufumene ukuba i-collagen eyonakeleyo yandisa inani le-arginine, i-amino acid esetyenziswa yi-enzyme nitric oxide synthase (iNOS) ukuvelisa i-compounds ebizwa ngokuba yi-reactive nitrogen iintlobo. (RNS). Oku, kwabangela ukuba abamelwane, iiseli ze-stellate ezixhasayo zakhe i-collagen-based meshes ejikeleze amathumba, batsho ababhali bophononongo.
"Iziphumo zethu zibonise indlela i-pancreatic tumors program macrophages ukufaka isandla ekwakhiweni kwemiqobo ye-fibrotic," kusho umbhali wokuqala wokufunda uMadeleine LaRue, PhD. Ngexesha lokufunda, uLaRue wayengumfundi ophumelele kwilebhu yombhali ophezulu wokufunda uDafna Bar-Sagi, PhD, uProfesa we-S. Farber we-Biochemistry kunye ne-Molecular Pharmacology kunye ne-Vice Dean yeSayensi kwi-NYU Langone Health. "Esi sikhokelo se-molekyuli sinokusetyenziselwa ukulwa notshintsho lomhlaza kwizicubu ezijikeleze amathumba," wongeza uLaRue.
Umhlaza wePancreatic ungoyena nobangela wesithathu wokusweleka okunxulumene nomhlaza e-United States, kunye nenqanaba lokusinda leminyaka emihlanu le-10%. Umhlaza wePancreatic uhlala unzima ukuwunyanga ubukhulu becala ngenxa yothungelwano olubanzi lweethishu zefibrotic ezijikeleze amathumba. Le nethiwekhi ayithinteli kuphela ukufikelela ngonyango, kodwa ikhuthaza ukukhula okunamandla.
Uphononongo lwangoku, iimvavanyo zibonise ukuba i-macrophages ekhulile kwisitya sezondlo (iinkcubeko), kwaye iguqulelwe kwi-cancer-tolerant setting (M2), yaphula i-collagen eninzi kune-macrophages ehlasela iiseli zomhlaza (M1). Ukuqhubela phambili, iqela liqinisekisile ngoluhlu lweemvavanyo ukuba i-M2 macrophages inamanqanaba aphezulu e-enzyme eyenza i-RNS, njenge-iNOS.
Ukuqinisekisa ezi zinto zifunyanisiweyo kwiimpuku eziphilayo, iqela lafaka iiseli ze-stellate ezinokuthi "zondliwa kwangaphambili" ngekholaji, okanye zigcinwe kwindawo engondliwayo, emacaleni ezilwanyana zophononongo kunye neeseli zomhlaza wepancreatic. Iqela liye labona ukwanda kweepesenti ezili-100 kubuninzi be-intra-tumoral collagen fibers kumathumba athathwe kwiiseli zomhlaza ezifakwe kunye neeseli ze-stellate ngaphambi kokuba ziphathwe nge-collagen.
Okubalulekileyo, uphononongo lubonise okokuqala ukuba i-macrophages kufuphi neeseli zomhlaza we-pancreatic, ayithathi nje kuphela kwaye iphule i-collagen eninzi njengenxalenye yokukhupha iiprotheni ezondla ukukhula okungaqhelekanga, kodwa zitshintshwa ngokutshabalalisa, ukuze inkqubo yabo yokucubungula amandla. (imetabolism) iphinda ifakwe kwiingcingo kunye nemiqondiso yokwakhiwa kwefibrotic.
"Iqela lethu lifumanise indlela edibanisa ukuguqulwa kwe-collagen kwisakhiwo sendawo enganyangekiyo kunyango malunga namathumba e-pancreatic," utshilo uBar-Sagi. "Njengoko le ndawo ixineneyo isesona sizathu siphambili sokuba kutheni umhlaza we-pancreatic ubulala kangaka, ukuqonda ngcono amakhonkco phakathi kokutyholwa kweeprotheyini kunye nokwakhiwa kwemiqobo yokukhusela kuya kufuneka ukuze kuphuculwe unyango lobu bubi butshabalalisayo."
