Age-associated changes of extracellular matrix collagen impair lung cancer cell migration.
Although advanced age is linked with an increased incidence of lung carcinomas, elderly patients develop fewer metastatic tumors than their younger counterparts. Since extracellular matrix controls carcinogenesis, we studied the effect of aged fibrillar collagen (rat tail) on the invasiveness of lung carcinoma cells (H322, H358). Two- and three-dimensional invasion assays revealed a reduced migration of lung cancer cells through a matrix of collagen from old (24 mo) compared with young (2 mo) or adult (12 mo) rats. This was most strongly observed for H322 cells, which had a better migration behavior than H358 cells. Since old collagen was increasingly modified by advanced glycation end products (AGEs; fluorescing AGEs, nonfluorescing carboxymethyllysine), we generated different AGE-collagens by treating collagen with ribose or alpha-dicarbonyls. Similarly to old collagen, AGE-collagen reduced the invasive migration of H322 cells. Subsequent analyses demonstrated that old and AGE-collagens impair distinct mechanisms contributing to cell migration, i.e., efficient cell adhesion and proteolytic degradation of collagen by membrane-type matrix metalloproteinase (MT-MMP; MT-MMP3 in H322 cells). Our data indicate that age-related alterations of the extracellular matrix contribute to a less invasive behavior of lung carcinoma cells, in which AGE modifications of aged collagen seem to play an important role.
Bartling
Babett
B
Department of Cardio-thoracic Surgery, University Hospital Halle (Saale), Ernst-Grube-Str. 40, 06120 Halle (Saale), Germany. babett.bartling@medizin.uni-halle.de
Desole
Maximilian
M
Rohrbach
Susanne
S
Silber
Rolf-Edgar
RE
Simm
Andreas
A
D000375:Aging / Q000473:pathology / Q000502:physiology*; D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D003094:Collagen / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D008297:Male; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism; D053513:Matrix Metalloproteinase 16 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D051381:Rats; D017207:Rats, Sprague-Dawley; D055752:Small Cell Lung Carcinoma / Q000503:physiopathology*; D014407:Tumor Cells, Cultured
D017127:Glycation End Products, Advanced; D003094:Collagen; D053513:Matrix Metalloproteinase 16; D053511:Matrix Metalloproteinase 14