▁for ▁further ▁cancer ▁pro gression ▁and ▁met ast asis ▁in ▁distant ▁org ans ▁and ▁t issues . ▁Mass ive ▁met ast atic ▁les ions ▁lead ▁to ▁the ▁development ▁of ▁severe ▁organ ▁failure ▁and , ▁therefore , ▁a ▁patient ’ s ▁death . ▁The ▁range ▁between ▁“ end ” ▁points ▁of ▁a ▁complex ▁invas ive ▁met ast atic ▁process ▁– in vas ion ▁of ▁the ▁primary ▁tum or ▁into ▁surrounding ▁t issues ▁and ▁the ▁formation ▁of ▁met ast atic ▁fo ci ▁– com pr ises ▁several ▁stages , ▁the ▁passage ▁of ▁which ▁is ▁strictly ▁necessary ▁for ▁the ▁successful ▁development ▁and ▁subsequent ▁pro gression ▁of ▁tum or ▁growth : ▁int ra vas ation , ▁surv ival ▁and ▁presence ▁in ▁the ▁system ic ▁circul ation , ▁extra vas ation ▁with ▁subsequent ▁colon ization ▁of ▁org ans ▁by ▁tum or ▁cells , ▁and ▁the ▁formation ▁of ▁clin ically ▁detect able ▁met ast asis . ▁T um or ▁growth ▁is ▁accompanied ▁by ▁increasing ▁pressure ▁on ▁ext rac ell ular ▁matrix ▁structures , ▁whereas ▁the ▁t issue ▁micro environment ▁f ights ▁to ▁retain ▁its ▁functional - an atomic ▁integrity ▁via ▁increasing ▁pressure ▁on ▁tum or ▁cells . ▁The ▁factors ▁limit ing ▁the ▁growth ▁of ▁m align ant ▁ne op las m ▁include ▁the ▁bas al ▁memb rane ▁and ▁various ▁components ▁of ▁the ▁surrounding ▁st rom a , ▁increased ▁inter st it ial ▁pressure , ▁limited ▁o xygen ▁supply ▁to ▁tum or ▁cells ▁and ▁the ▁formation ▁of ▁active ▁o xygen ▁forms , ▁hy po x ia ▁conditions , ▁and ▁permanent