Alterations of basement membrane in di-isopropanolnitrosamine- induced carcinogenesis of the rat thyroid gland: an immunohistochemical study

Abstract

Alterations of basement membrane (BM) in di-isopropanolnitrosamine (DIPN)-induced carcinogenesis of the rat thyroid gland were examined by means of immunohistochemical localization of collagen type IV (CN-IV), laminin (LN), and fibronectin (FN) in prenodular and nodular thyroid lesions, correlating with the morphogenesis and proliferative activity of these lesions. Adult male rats of the Wistar strain were injected s.c. in the back with DIPN, and the thyroid glands were removed at the 15th and 30th week of treatment. Each of 133 thyroid lesions was histochemically analyzed. The follicular epithelial BM as revealed by CN-IV and LN was discontinued or completely lost during the progression of thyroid lesions from pre-nodular to nodular lesions and finally overt carcinomas. At the same time, the BM of vascular endothelial cells demonstrated a loss of dense capillary networks of follicles, a sinusoidal dilatation and, predominantly in carcinomas, development of interstitial-type blood vessels. However, FN, which was hardly stained in the normal thyroid tissue, was remarkably deposited in the interstitium of invasive carcinomas. These observations strongly suggested that alterations of BM structure play a key role in the morphogenesis of rat thyroid tumors, and that the expression of FN is an important step in the invasive growth of thyroid tumors.

Characterisation of the progression of azaserine-induced rat pancreatic adenocarcinoma by proliferative cell nuclear antigen, basement membrane laminin and trypsinogen immunohistochemistry

“…The reversal of the initial gradual BML loss in the month 13 adenomas and the subsequent decrease to the month 20 differentiated ACs (Table 3) are closely parallel with the trends in changes of the PCNA indices, i.e. The trend of gradually decreasing laminin expression manifested in an increasingly discontinuous BM was also observed in other tumours induced in mouse uterine cervix (Rubio and Biberfeld 1979), rat colon (Ljubimov and Krutovskikh 1987), mouse skin (Köpf-Maier and Flug 1996) and rat thyroid gland (Lu et al 2000). This assumption is in line with the known adhesion dependency of proliferation of non-malignant cells.…”

“…It was suggested that laminin may take part in promotion of invasion (Lohi 2001). murine uterine cervix (Rubio and Biberfeld 1979) and skin (Köpf-Maier and Flug 1996), rat colon (Ljubimov and Krutovskikh 1987) as well as mouse and rat thyroid gland (Lu et al 2000). murine uterine cervix (Rubio and Biberfeld 1979) and skin (Köpf-Maier and Flug 1996), rat colon (Ljubimov and Krutovskikh 1987) as well as mouse and rat thyroid gland (Lu et al 2000).…”

Three-dimensional context regulation of metastasis

“…Tumor cell growth can be suppressed and cells can be induced to re-form polarized epithelium when they come into contact with intact BM in vivo or are cultured on intact BM in vitro [92, 95, 96, 112]. Structural alterations in the BM occur early on in cancer, even before the development of a palpable tumor [113]. These include gaps, thickening, loosening of cells from each other and the surrounding stroma [90], and can be considered a hallmark of malignant invasion because tumors surrounded by an intact BM generally do not penetrate into surrounding tissues [114–116].…”

Can cancer be reversed by engineering the tumor microenvironment?

“…Interestingly, although stable adult epithelial tissues do not normally exhibit major changes in ECM structure or undergo active changes in form, ultrastructural changes in the basement membrane do occur during early phases of cancer formation, prior to development of a palpable tumor [81] [82,83]. These structural alterations include the appearance of basement membrane gaps, thickening and reduplication, as well as loosening of basal cells from one another and from neighboring connective tissue [81].…”

“…These structural alterations include the appearance of basement membrane gaps, thickening and reduplication, as well as loosening of basal cells from one another and from neighboring connective tissue [81]. Experimental treatment of thyroid gland with carcinogens similarly causes the epithelial basement membrane to become discontinuous (as seen in the tips of growing epithelial buds in the embryo), and then to completely dissolve in certain regions as the lesions progress from pre-nodular to nodular forms, and finally to overt invasive carcinomas [82].…”