Impact of carbamylation and glycation of collagen type I on migration of HT1080 human fibrosarcoma cells.

Collagen type I is an abundant component of the extracellular matrix and due to its longevity, constitutes a prominent target of non-enzymatic post-translational in vivo modifications such as carbamylation and glycation. These protein modifications involved in aging, renal diseases and diabetes, are linked to elevated cancer risk. In this in vitro study, we investigated the impact of carbamylated and glycated collagen type I on the migratory behavior of the highly invasive HT1080 human fibrosarcoma cells. The proliferation of HT1080 on modified collagens did not differ from that on native form. The glycated collagen delayed the cell adhesion time whereas the carbamylated one had no effect. The migration ability of HT1080 was studied by quantifying single cell speed using videomicroscopy. Glycation strongly inhibited mean cell speed by 47% whereas carbamylation moderately affected it by 12%. In addition, the influence of these collagen modifications on actin and vinculin organization was studied. On the glycated collagen, 63% of cells revealed a dramatic loss of actin stress fibers vs. 28% on the carbamylated one. In these cells, disorganized F-actin was accompanied with a disturbance of vinculin and both proteins were localized at the rim of the cells. Concerning the focal adhesion kinase (FAK) expression, glycated collagen only induced a significant inhibition. Whereas, both collagen modifications provoked a differential inhibition of FAK phosphorylation state by 25% for carbamylation and 60% for glycation. In conclusion, our data suggest that, in vivo, collagen glycation and carbamylation may affect tumor cell metastasis. This suggestion is supported by clinical studies reporting less aggressive tumors in diabetic or uremic patients. Consequently, the impact of such post-translational modifications has to be taken into account in order to better understand the link between aging, diabetes or uremia and cancer progression.

[1]  T. Lyons,et al.  Accumulation of Maillard Reaction Products in Skin Collagen in Diabetes and Aging a , 1992, Annals of the New York Academy of Sciences.

[2]  E. Golemis,et al.  Fibroblast-derived 3D matrix differentially regulates the growth and drug-responsiveness of human cancer cells. , 2008, Matrix biology : journal of the International Society for Matrix Biology.

[3]  N. Dubrawsky.  Cancer statistics , 1989, CA: a cancer journal for clinicians.

[4]  H. Mori,et al.  Renal cell carcinoma in dialysis patients: A single center experience , 2006, International journal of urology : official journal of the Japanese Urological Association.

[5]  J. Bijlsma,et al.  Effect of Collagen Turnover on the Accumulation of Advanced Glycation End Products* , 2000, The Journal of Biological Chemistry.

[6]  Philippe Gillery,et al.  Evaluation of nonenzymatic posttranslational modification-derived products as biomarkers of molecular aging of proteins. , 2010, Clinical chemistry.

[7]  Danielle T. Loughlin,et al.  Modification of Collagen by 3-Deoxyglucosone Alters Wound Healing through Differential Regulation of p38 MAP Kinase , 2011, PloS one.

[8]  Maddy Parsons,et al.  Advances in imaging cell–matrix adhesions , 2010, Journal of Cell Science.

[9]  R. G. Paul,et al.  The effect of advanced glycation end-product formation upon cell-matrix interactions. , 1999, The international journal of biochemistry & cell biology.

[10]  R. G. Paul,et al.  Glycation of collagen: the basis of its central role in the late complications of ageing and diabetes. , 1996, The international journal of biochemistry & cell biology.

[11]  V. Monnier,et al.  Intervention against the Maillard reaction in vivo. , 2003, Archives of biochemistry and biophysics.

[12]  A. Eckhardt,et al.  Study of posttranslational non-enzymatic modifications of collagen using capillary electrophoresis/mass spectrometry and high performance liquid chromatography/mass spectrometry. , 2007, Journal of chromatography. A.

[13]  Martin A. Schwartz,et al.  Cell adhesion: integrating cytoskeletal dynamics and cellular tension , 2010, Nature Reviews Molecular Cell Biology.

[14]  S. Ricard-Blum,et al.  Impact of carbamylation on type I collagen conformational structure and its ability to activate human polymorphonuclear neutrophils. , 2006, Chemistry & biology.

[15]  Jihe Zhao,et al.  Signal transduction by focal adhesion kinase in cancer , 2009, Cancer and Metastasis Reviews.

[16]  S. Poitevin,et al.  Human Blood Monocytes Interact with Type I Collagen Through αxβ2 Integrin (CD11c-CD18, gp150-95)1 , 2000, The Journal of Immunology.

[17]  A. Kraus,et al.  Essential carbamoyl-amino acids formed in vivo in patients with end-stage renal disease managed by continuous ambulatory peritoneal dialysis: isolation, identification, and quantitation. , 1998, The Journal of laboratory and clinical medicine.

[18]  Z. Rasheed,et al.  Non-enzymatic glycation of proteins: From diabetes to cancer , 2009, Biomeditsinskaia khimiia.

[19]  A. Kraus,et al.  Carbamoylation of amino acids and proteins in uremia. , 2001, Kidney international. Supplement.

[20]  T. Habuchi,et al.  Renal cell and transitional cell carcinoma in a Japanese population undergoing maintenance dialysis. , 2005, The Journal of urology.

[21]  J. Baynes,et al.  Glycoxidation and lipoxidation in atherogenesis. , 2000, Free radical biology & medicine.

[22]  Christoph Ballestrem,et al.  Vinculin controls focal adhesion formation by direct interactions with talin and actin , 2007, The Journal of cell biology.

[23]  S. Rohrbach,et al.  Age‐associated changes of extracellular matrix collagen impair lung cancer cell migration , 2009, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[24]  Li Yan,et al.  Impairment of human keratinocyte mobility and proliferation by advanced glycation end products-modified BSA , 2011, Archives of Dermatological Research.

[25]  Marie Guilbert,et al.  3D collagen type I matrix inhibits the antimigratory effect of doxorubicin , 2010, Cancer Cell International.

[26]  K. Urabe,et al.  Migration of keratinocytes is impaired on glycated collagen I , 2005, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[27]  M. Socinski,et al.  Bronchogenic Cancer, Metastases, and Aging , 1983, Journal of the American Geriatrics Society.

[28]  L. Gaber,et al.  Carbamoylation of glomerular and tubular proteins in patients with kidney failure: a potential mechanism of ongoing renal damage. , 2001, Swiss medical weekly.

[29]  Alan W. Stitt,et al.  Advanced glycation of the Arg-Gly-Asp (RGD) tripeptide motif modulates retinal microvascular endothelial cell dysfunction , 2009, Molecular vision.