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ADIPOSE TISSUE EXTRACELLULAR MATRIX REMODELLING IN CANCER CACHEXIA
Author(s) -
Alves Michele,
Matos Neto Emidio,
Maximiliano Linda,
Alcantara Paulo,
Otoch Jose,
Batista Miguel,
Seelaender Marilia
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.925.7
Subject(s) - adipose tissue , extracellular matrix , immunostaining , collagen vi , fibronectin , cachexia , fibrosis , laminin , sirius red , cancer , pathology , white adipose tissue , chemistry , medicine , cancer research , endocrinology , immunohistochemistry , biochemistry
Cachexia is a paraneoplastic syndrome in which white adipose tissue (WAT) suffers profound wasting. WAT alterations that may lead to extracellular matrix (ECM) rearrangement. AIM: to assess the effects of cachexia upon ECM of subcutaneous adipose tissue (SAT) by examining the expression of collagens IIIα1 (COL3A1), VIα1 (COL6A1) and fibronectin (FN1).
Methods Patients of the University Hospital were enrolled in 2 groups: Cachectic cancer (CACS,n=14)(gastrointestinal tumours) and Control (C, n=8) (hernia). One gram of SAT was collected in surgery and fixed in 4% formaldehyde and paraffin embedded. The sections (5µm) were stained by Picro Sirius red (PS) for polarized light microscopy, or employed for immunostaining, when slides were incubated with the antibodies overnight (4ºC). Gene expression analysis was performed by RTqPCR and normalised to reference gene 18s.
Results PS stain demonstrated a strong presence of collagen in the SAT of CACS, and preserved ECM architecture was observed in C. Increased amounts of COL3A1 were found in CACS, despite no changes in gene expression. Immunostaining for COL6A1 was modified in CACS, with collagen aggregates in fibrotic areas and increased mRNA levels of COL6A1 (p<0.05). FN1 labelling was most evident in concomitance to augmented mRNA levels in CACS, comparing with C.
Conclusions Cancer cachexia deeply affects SAT organization, causing accumulation of ECM components in the adipose pad leading to remodelling during cachexia. The increase of COL3A1, COL6A1 and FN1 may be directly related with the emergence of tissue fibrosis.
Ethics: ICB/USP(788);HU/USP(752/07). Funding: FAPESP (012/50079‐0).