Elevated levels and fragmented nature of cellular fibronectin in the plasma of gastrointestinal and head and neck cancer patients.
BACKGROUND
Tumor invasion occurs following enzymatic degradation of components of the extracellular matrix. The proteolysis-resistant domains of matrix components are likely to appear in the blood plasma during invasion, and could be used as markers of malignancy. Cellular fibronectin (cFN), a major ECM component, possesses 3 alternately spliced principal protease resistant domains; two of which, extra domain A (EDA) and III connecting segment (IIICS), were selected for this study of the nature of the plasma cFN molecules and its levels in normal subjects (n=51), and patients with gastrointestinal (G-I, n=145) or head and neck (H-N, n=127) cancers.


METHODS
ELISA was used to measure the cFN levels in plasma and Western blotting to analyze its fragmented nature in plasma samples from normal individuals and patients with G-I or H-N cancers.


RESULTS
cFN in blood plasma, as probed by anti-EDA and anti-IIICS antibodies on Western blots, is found to exist entirely in a fragmented form in normal subjects and G-I and H-N cancer patients. The cFN polypeptides in plasma have Mr of 160 and 100. The levels of plasma cFN, determined by ELISA using the 2 antibodies, are found to be increased in G-I and H-N cancers. In a significant number of stomach (43%), gall bladder (35%) and colon (17%) cancer cases an additional anti-EDA-reactive 30 kD peptide is seen in the plasma.


CONCLUSIONS
The mean rise for all sites is statistically significant, and 65% of all patients show cFN levels >80th percentile of normal values. The characterization of the 30 kD peptide showed that it does not contain the IIICS domain and also lacks the central cell- and heparin-binding sites.
Warawdekar
Ujjwala M
UM
Biochemistry and Cell Biology, Advanced Centre for Treatment, Research and Education in Cancer, Kharghar, Navi Mumbai 410 208, India. uwarawdekar@actrec.res.in
Zingde
Surekha M
SM
Iyer
K S N
KS
Jagannath
P
P
Mehta
Ashok R
AR
Mehta
Narendra G
NG
D000595:Amino Acid Sequence; D015153:Blotting, Western; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005353:Fibronectins / Q000097:blood* / Q000737:chemistry; D005770:Gastrointestinal Neoplasms / Q000097:blood*; D006258:Head and Neck Neoplasms / Q000097:blood*; D006801:Humans; D008969:Molecular Sequence Data
D005353:Fibronectins