Oncogenic Ras-transformed human fibroblasts exhibit differential changes in contraction and migration in 3D collagen matrices.
Tractional force exerted by tissue cells in 3D collagen matrices can be utilized for matrix remodeling or cell migration. The interrelationship between these motile processes is not well understood. The current studies were carried out to test the consequences of oncogenic Ras (H-Ras(V12)) transformation on human fibroblast contraction and migration in 3D collagen matrices. Beginning with hTERT-immortalized cells, we prepared fibroblasts stably transformed with E6/E7 and with the combination HPV16 E6/E7 and H-Ras(V12). Oncogenic Ras-transformed cells lost contact inhibition of cell growth, formed colonies in soft agar and were unable to make adherens junctions. We observed no changes in the extent or growth factor dependence of collagen matrix contraction (floating or stress-relaxation) by oncogenic Ras-transformed cells. On the other hand, transformed cells in nested collagen matrices lost not only growth factor selectivity, but also cell-matrix density-dependent inhibition of migration. These findings demonstrate differential regulation of collagen matrix contraction and cell migration in 3D collagen matrices.
Menezes
Gustavo C
GC
Universidade Federal do Rio de Janeiro, Instituto de Biofisica Carlos Chagas Filho, Rio de Janeiro, Brazil.
Miron-Mendoza
Miguel
M
Ho
Chin-Han
CH
Jiang
Hongmei
H
Grinnell
Frederick
F
D000818:Animals; D018929:Cell Culture Techniques; D002465:Cell Movement / Q000502:physiology*; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D011905:Genes, ras; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
D009856:Oncogene Proteins, Viral; D003094:Collagen; D018631:ras Proteins