Premium
Macromolecular Distribution Volume in Human Ovarian and Endometrial Cancer
Author(s) -
Wiig Helge,
HasleneHox Hanne,
Oveland Eystein,
Woie Kathrine,
Salvesen Helga,
Tenstad Olav
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.792.3
Subject(s) - macromolecule , chemistry , distribution (mathematics) , albumin , extracellular matrix , ovary , ovarian cancer , biophysics , biochemistry , pathology , biology , medicine , cancer , endocrinology , mathematical analysis , mathematics
Elements of the extracellular matrix (ECM), notably collagen and glucosaminoglycans, will restrict part of the space available for soluble macromolecules because the molecules cannot occupy the same space. This phenomenon may influence macromolecular drug uptake. To study the influence of steric and charge effects of the ECM on the distribution volumes of macromolecules in human healthy and malignant gynecologic tissues we used as probes 15 abundant plasma proteins quantified by high‐resolution mass spectrometry. The available distribution volume (V A ) of albumin was increased in ovarian carcinoma compared with healthy ovarian tissue. Furthermore, V A of plasma proteins between 40 and 190 kDa decreased with size for endometrial carcinoma and healthy ovarian tissue, but was independent of molecular weight for the ovarian carcinomas. An effect of charge on distribution volume was only found in healthy ovaries, which had lower hydration and high collagen content, indicating that a condensed interstitium increases the influence of negative charges. A number of earlier suggested biomarker candidates were detected in increased amounts in malignant tissue, showing that interstitial fluid, even when unfractionated, can be a valuable source for tissue‐specific proteins. We demonstrate that the distribution of abundant plasma proteins in the interstitium can be elucidated by mass spectrometry methods and depends markedly on hydration and ECM structure. Our data can be used in modeling of drug uptake, and give indications on ECM components to be targeted to increase the uptake of macromolecular substances.