Qualitative and Quantitative Analysis of Tumour Invasion in vivo and in vitro

Abstract

epa rtm en t o f R adiotherapy a n d N u cle a r M edicine, U niversity H ospital and 2 Laboratory o f M olecular Biology (F .M .V .R .), S ta te U niversity Ghent, B-9000 Ghent, Belgium SUMMARYQualitative and quantitative methods for the analysis of invasion in 'natural' and in experimental tumours in vivo and in vitro are reviewed. In human tumours the functional consequences of invasion were evaluated histologically through staging on the basis of depths of invasion and through the presence of tum our cells inside vessels. Antibodies against components of the basement membrane have facilitated the definition of m inim al invasion. W ith new probes derived from oncogene research the search for molecular differences between invasive and non-invasive parts of the tum our has begun. Since the same methods as those used for analysis of natural tumours also apply to experimental tumours in vivo , the major advantage of the latter is the possibility of manipulation. We have described a new mesenterium assay that may permit the selection of invasive cells from non-invasive ones in transfection experiments. Invasion relative to growth as a function of time was quantified in the kidney invasion test. In three-dimensional confrontations between embryonic chick heart fragments and invasive cells, we have used both a subjective grading and a qualitative computer-assisted image analysis of serial histological sections to score invasion. In two-dimensional confrontations supplementary methods could be applied, since such confrontations permitted direct observations on living cultures. In a variety of natural and experimental tumours, ultrastructural analysis, transmigration in two-compartment chambers, and release of metabolic label have demonstrated the role of motility and of lytic activity in tumour invasion.

In vivo and in vitro invasion in relation to phenotypic characteristics of human colorectal carcinoma cells

“…The confronting pairs were fixed, embedded in paraffin and sectioned for microscopy after 4 and 7 days. Invasiveness was determined and scored as described previously (Mareel et al, 1987).…”

“…In any case, invasion, defined as the ability of carcinoma cells to traverse the basement membrane (BM), detach from the pnmary tumour and migrate into the extracellular matrix (ECM), is an important step. Various in vitro models have been developed to study invasion (Mareel et al, 1987), including invasion of tumour cells into embryonic chick heart fragments (Mareel et al, 1979).…”

Morphotypic plasticity in vitro and in nude mice of epithelial mouse mammary cells (NMuMG) displaying an epithelioid (e) or a fibroblastic (f) morphotype in culture

“…For cell lines of fibroblastic origin, a good correlation was found between invasion in vitro and in vivo, but for cells of epithelial origin many exceptions were found [18,19]. Differences in invasive phenotype between cells growing in vivo compared with in vitro cultures have led to the micro-ecosystem concept.…”

Screening for Invasion of the Individual Human Brain Tumour in an Autologous Confrontation System in vitro

“…On the one hand, some methods look for the interaction between one specific component of the host tissue and tumour cells such as invasion in extracellular matrix [1], in reconstructed basement membranes [2], in collagen gels [3], in matrigel [4,5] and in gel sponges [6,7]. On the other hand, heterologous organ fragments of embryonic origin such as chick mesonephros [8,9], chick heart [10], thyroid [11], rat brain aggregates [12] are used.…”