The basement membrane, immune cells, capillaries, fibroblasts and extracellular matrix (ECM) constitute the tumour stroma, commonly referred to as the ‘reactive stroma’. The fibroblasts from the initial stages of a tumour, as the main constituents of the reactive stroma, present a different phenotype from the normal fibroblasts and play a crucial role in tumour progression. This review presents the differences between normal and tumour stromal fibroblasts and analyzes the molecular mechanisms (which involve growth factors, ECM components, matrix metalloproteinases, integrins and cell adhesion molecules) in the complex interactions between stromal fibroblasts and tumour cells. To date, several examples of heterotypic interactions between tumour stromal fibroblasts and tumour cells have supported the hypothesis that the tumour stroma promotes the growth of the tumour mass, as well as invasion and metastasis. However, it remains possible that the stroma acts essentially as a local modulator to impede tumorigenesis at an early stage and that the desmoplastic response is a host defence reaction designed to confine the developing tumour. The latter hypothesis has largely been neglected. The review aims to give a broader view on the role of stromal fibroblasts in tumour growth, invasion and metastasis.

The disturbance of the growth control mechanisms in tumour cells in vivo may be manifested as uncontrolled growth of the tumour stroma in vitro. Stromal fibroblast-like finite cell lines produced from benign or malignant human breast tissue specimens exhibited cell overlapping which ranged from multilayers to dense piling up colonies, while cells derived from normal tissues exhibited intense contact inhibition of growth and locomotion, under the same culture conditions. 6 out of 13 lines derived from malignant tissues and 2 out of 5 lines derived from benign lesions exhibited the phenomenon of ‘periodic appearance of piling up colonies’.

Cocultivation of human fibroblasts and HeLa cells in vitro leads to the development of specific patterns of growth. These patterns depend on the cell density and cell-cell ratio in the initial mixed inoculum. Human fibroblasts can cause extensive nuclear fragmentation and cellular disintegration of HeLa cells in vitro after coculture for periods longer than 10 days, without subculturing, and with medium replacement every 2 days. This phenomenon is preceded by directional locomotion of the fibroblastic population parallel to the edges of and around HeLa colonies and by overgrowth of both cell types at the border sites. A dense border is thus developed around the HeLa colonies. In the absence of refeeding every 2 days, HeLa cells can overgrow, pass the dense border and form a new zone. Refeeding at this stage can again cause the formation of a second concentric dense border around the HeLa zone. This phenomenon may represent an in vitro metaphor of the invasive property of neoplastic cells. It also points out, however, the importance of feeding for the activation of fibroblasts against HeLa cells.

In a series of 109 Greek patients with breast carcinoma, a significant increase in the haptoglobin type 1–1 was observed.

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