The development of an altered stromal microenvironment is a common feature of many tumours including squamous cell carcinoma (SCC), and there is increasing evidence that these changes in the stroma, which include increased expression of proteases and cytokines, may actually promote tumour progression. A common finding is that stromal fibroblasts become 'activated' myofibroblasts, expressing smooth muscle actin and secreting cytokines, proteases and matrix proteins. We show that myofibroblasts are commonly found in the stroma of oral SCC and are often concentrated at the invasive margin of the tumour. Using oral SCC cells and primary oral fibroblasts, we demonstrate that tumour cells directly induce a myofibroblastic phenotype, and that this transdifferentiation is dependent on SCC-derived TGF-b1. In turn, myofibroblasts secrete significantly higher levels of hepatocyte growth factor/scatter factor compared with fibroblast controls, and this cytokine promotes SCC invasion through Matrigel, a mixture of basement membrane proteins. This is the first time that this double paracrine mechanism has been demonstrated between squamous carcinoma cells and fibroblasts, and emphasises that cancer invasion can be promoted indirectly by the release of tumour-induced host factors from stroma.

This study supports the presence of an association between high 25(OH)D levels during the years preceding disease onset and a decreased risk of MS. In the very limited material with samples drawn in early pregnancy, where month-of-birth effects were controlled for, we found no association between gestational 25(OH)D levels and MS risk in the offspring. Decreasing 25(OH)D levels in the population may contribute to explain the increasing MS incidence that is suggested from epidemiologic studies.

Integrins are a family of heterodimeric cell surface receptors, which are expressed on most cells where they mediate cell-cell and cell-extracellular matrix (ECM) interactions. The alphavbeta6 integrin is epithelial-specific and binds to the ECM proteins fibronectin, vitronectin and tenascin, and also to the latency associated peptide of TGF-beta. Unlike most epithelial integrins, alphavbeta6 is not expressed constitutively by healthy oral epithelia, but is up-regulated during tissue remodelling, including that accompanying wound healing and carcinogenesis. Although, the data at present have been generated principally from in vitro studies, there is increasing evidence to suggest that alphavbeta6 may promote carcinoma progression: alphavbeta6 has been shown to modulate invasion, inhibit apoptosis, regulate protease expression and activate TGF-beta1. This review examines the current literature, and discusses the possible role of alphavbeta6 in wound healing, and in the development and progression of oral squamous cell carcinoma.

Tumour invasion is a dynamic process occurring in three dimensions and involving interactions between both tumour and stromal cells. Experimental analysis of squamous carcinoma cell invasion has often used the organotypic gel culture system, which is generated by plating tumour cells on to a synthetic stroma composed of a collagen gel embedded with fibroblasts. Unfortunately, quantitation of invasion in these organotypic gels has relied largely on subjective pathological opinion, which may be influenced by different patterns of tumour cell infiltration. Therefore a computer-assisted digital image analysis system that assesses invasion objectively and provides a numerical 'Invasion Index' was developed. The Invasion Index, by combining depth and pattern of invasion in a single value, establishes a quantitative value that allows assessment of the influences of positive and negative regulation of tumour invasion. These data demonstrate that the organotypic gel system is a robust, accurate, and reproducible method for measuring tumour cell invasion. They also show that the Invasion Index can be used after organotypic gels have been implanted in mice for up to 6 weeks. Illustrative examples of how various factors influence the invasion of squamous carcinoma cells in three dimensions both in vitro and in vivo are provided.