// what we showed them // [node] // -> = edge // {nodes together} primary [P] detachment [A] invasion [I] breach ecm [R] intravasation [V] [B] = {I, R, V} motility [O] migration [T] [C] = {O, T} extravasation [D] colonization [L] proliferation [X] angiogenesis [N] [E] = {L, X, N} micrometastasis [F] macrometastasis [G] // other steps/nodes suggested by experts // ... = they said "and then the rest", so agreed with the diagram we showed them but did not explicitly mentioned the steps // node' = different wording/description for that node // node? = uncertain // * = implicit node vessel infiltration [J] interactions with stroma [K] events at primary [H] something happens to cell [M] EMT starts [Ui] EMT [U] lymph-&angio-genesis starts [Ni] lymph-&angio-genesis [N] ECM remodeling [ER] progressive growth [PG] [PG] = [E'] [Ei...n] = {E1, E2, E3, E4… En} go somewhere [GS] survival in circulation [SC] energy perturbations [EP] metastatic niche [MN] trigger [TR] oligometstasis [Q] wide metastasis [WM] metastatic seeding [Z] floating around [FA] adhesion [S] MET [W] in bloodstream [BL] [BL] = [FA'] =[SC'] [H] = {P, M} // what we showed them P -> A -> B -> C -> D -> E -> F -> G // 28 P -> {A, B, C} -> D -> {E1, E2, E3, E4… En} -> F* -> G* // 27 P -> A -> B -> C -> D -> E -> F -> N -> G // 26 P -> U? -> {A, U?, N?} -> {B, U?, N?} -> {C, N?} -> {D?, N?} -> {E, N?} -> {F, N?} -> {G, N?} // 25 P -> A -> ? -> E -> -> G* // 24 P* -> A* -> N -> B -> C* -> D* -> E* -> F* -> G* // 23 P -> M? -> A -> {I, R?, V} -> {O, T?} -> D? -> E -> F* -> G* P -> M? -> A -> ? -> E -> F* -> G* // in colorectal M? = U // 22 P -> A -> B -> SC -> D -> E -> F* -> G* // 21 P -> A -> T -> B -> T? -> D -> E* -> F* -> G* // 20 P -> A -> C -> I -> V? -> D? -> E -> F -> G // 19 // in ovarian cancer: no intravasation/extravasation P -> A -> B -> C -> D? -> C? -> E -> F -> G // 18 P* -> {A, B, C} -> D -> E -> F* -> G* // 17 P -> A? -> B -> {C, SC} -> MN -> E -> F -> G P* -> A* -> B* -> C* -> D -> TR -> E -> F* -> G* // 16 P* -> {A, ER?} -> C -> V -> D -> E* -> F* -> G* P* -> A -> C -> B -> C* -> D* -> E* -> F* -> G* {P, K} -> {A, ER} -> C -> B -> {SC, EP} -> D -> E -> {F, K} -> {G, K} -> {Q, K} -> {WM, K} // 15 P -> GS -> PG -> F* -> G* // 14 P -> Z -> L -> F* -> G* // in leukemia BL -> L -> F* -> G* // 13 P -> A -> FA -> T -> L -> F -> G // in ovarian cancer, extravasation, proliferation and angiogenesis are not as important // 12 H -> U -> ? -> W -> L -> F* -> G* // 11 P -> {A, C} -> B -> {L, X, N?} -> F -> N? -> G {A, B, C} = [U] // 10 P -> C -> {A, B} -> D -> MN -> E -> F* -> G* // 09 P -> A -> S -> E -> F* -> G* // 08 P* -> A* -> C -> B -> D* -> E* -> F* -> G* P -> A -> C -> B -> D* -> E* -> F* -> G* P* -> C -> A -> B -> D* -> E* -> F* -> G* // 07 // no order given, just the existence on some steps A I O ... // 6 {P, K} -> {A, B, C} -> D* -> E* -> F* -> G* // 5 P -> N -> A -> B* -> C* -> D* -> E* -> F* -> G* // 4 P -> A -> C -> B -> SC -> D -> E* -> F* -> G* // 3 (no comments) // 2 P -> ? -> PG -> F -> G* // 1 P -> A -> I -> E -> F* -> G*