Hyaluronan, TSG-6, and inter-α-inhibitor in periprosthetic breast capsules: reduced levels of free hyaluronan and TSG-6 expression in contracted capsules.
BACKGROUND
The exact mechanism of capsular contracture (CC) is still unknown. The covalent modification of hyaluronan (HA) with the heavy chains (HC) of inter-α-inhibitor (IαI) has been identified as an important pathway in inflammation and tissue remodeling, where HC·HA formation is catalyzed by TSG-6 (the protein product of tumor necrosis factor stimulated gene-6).


OBJECTIVE
The authors quantitatively assess the correlation between severity of CC (measured by Baker grade) and expression of HA, TSG-6, and IαI (ie, the polypeptides HC1, HC2, and bikunin) in periprosthetic breast capsules.


METHODS
Immunofluorescent staining for HA, TSG-6, HC1, HC2, and bikunin was carried out on periprosthetic breast capsules (n = 7) of each Baker grade from four anatomical locations. Quantitative analysis was performed to identify differences in staining intensity. Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to determine differences in TSG-6 gene expression levels.


RESULTS
Severity of contracture was associated with reduced staining for both free HA (Pearson correlation coefficient, r = -0.645, P < .001) and TSG-6 (r = -0.642, P = .002). RT-qPCR showed a significant negative correlation between severity of contracture and TSG-6 gene expression levels (r = -0.750, P = .001).


CONCLUSIONS
The negative correlation between TSG-6 expression levels and severity of CC suggests a possible protective role for TSG-6 in the context of CC formation, and this may have a clinically relevant role in prevention of breast CC.
National Institute for Health Research and Plastic & Reconstructive Surgery Research, University of Manchester, 131 Princess Street, Manchester, UK.
Kian T
KT
Tan
Andrew D
AD
Baildam
Ali
A
Juma
Caroline M
CM
Milner
Anthony J
AJ
Day
Ardeshir
A
Bayat
D000328:Adult; D000510:Alpha-Globulins / Q000235:genetics / Q000378:metabolism; D018427:Breast Implants / Q000009:adverse effects*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D006801:Humans; D006820:Hyaluronic Acid / Q000235:genetics / Q000378:metabolism; D057910:Implant Capsular Contracture / Q000473:pathology*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012720:Severity of Illness Index
D000510:Alpha-Globulins; D015815:Cell Adhesion Molecules; C072273:TNFAIP6 protein, human; C011877:inter-alpha-inhibitor; D006820:Hyaluronic Acid
J Biol Chem. 2009 Jul 24;284(30):20136-46
19491101
Plast Reconstr Surg. 2004 Jul;114(1):229-36
15220598
Breast J. 2003 Sep-Oct;9(5):428
12968969
Trends Immunol. 2005 Dec;26(12):637-43
16214414
Biochem Soc Trans. 2006 Jun;34(Pt 3):446-50
16709183
Osteoarthritis Cartilage. 2008 Nov;16(11):1343-55
18524635
Osteoarthritis Cartilage. 2001 Jan;9(1):42-8
11178946
J Cell Biol. 1992 Jan;116(2):545-57
1730767
Development. 2003 May;130(10):2253-61
12668637
J Biol Chem. 2003 Aug 29;278(35):32710-8
12799384
N Engl J Med. 1997 Mar 6;336(10):677-82
9041097
Am J Respir Cell Mol Biol. 2007 Jan;36(1):20-31
16873769
Aesthetic Plast Surg. 2005 Nov-Dec;29(6):510-8
16328636
Plast Reconstr Surg. 2006 Jul;118(1):224-9
16816700
J Biol Chem. 2005 Jul 8;280(27):25674-86
15840581
Ann Plast Surg. 1994 Jul;33(1):1-5
7944186
J Biol Chem. 2006 Jul 21;281(29):20303-14
16702221
Tissue Eng. 2006 Jul;12(7):1955-70
16889525
Ann Plast Surg. 2007 Feb;58(2):212-4
17245152
Plast Reconstr Surg. 2007 Jul;120(1):275-284
17572576
Plast Reconstr Surg. 1995 Oct;96(5):1119-23; discussion 1124
7568488
Arch Pathol Lab Med. 2002 Jun;126(6):727-30
12033966
Br J Plast Surg. 1993 Oct;46(7):547-56
8252260
J Biol Chem. 2001 Apr 27;276(17):13847-51
11278699
J Urol. 2001 May;165(5):1687-92
11342956
J Cell Sci. 2003 May 15;116(Pt 10):1863-73
12692188