Investigations into the mechanisms of growth of bloodborne tumour cells at sites of healing and regeneration

Loizidou, Marilena Christou (1992) Investigations into the mechanisms of growth of bloodborne tumour cells at sites of healing and regeneration. University of Southampton, Doctoral Thesis.

Abstract

The growth of bloodborne tumour cells in the liver was investigated using a partial hepatectomy (PH) model in rats. Two distinct tumour patterns were observed relating to the time interval between PH and tumour cell delivery. When tumour cells were introduced up to 2 days after PH, tumour grew as a mass at the excision scar; this was attributed to the facilitating effect of trauma on tumour growth. Later times of delivery (3-7 days after PH) gave rise to multiple internal and superficial tumour foci in the regenerating lobes, but no tumour mass at the scar; this was attributed to a facilitating effect of regeneration on tumour growth. Trapping experiments indicated a roughly uniform distribution of tumour cells throughout the liver. Therefore, the presence of tumour mass at the scar was not due to preferential trapping. Cell population studies showed that non-hepatocytes (mesenchymal and endothelial cells) proliferated maximally at 3 and 4 days after PH. Growth factor profiles revealed a peak of heparin binding growth factor at day 2, preceding the proliferation of non-hepatocytes. Non-hepatocytes were prepared from regenerating livers and characterised in vitro. Non-hepatocytes from livers at times of susceptibility to tumour growth in the parenchyma proliferated maximally in vitro. At other times such cells were quiescent. The proliferating population was characterised as fibroblastoid. The same highly proliferating cells significantly enhanced the growth of human colorectal cancer cells in an in vivo xenograft model. In conclusion, the enhanced tumour take at the scar and within the regenerating parenchyma were caused by distinct cellular mechanisms. Furthermore, there was a temporal relationship between the susceptibility of the regenerating liver to tumour growth, the production of growth factors and the appearance and behaviour of highly proliferating fibroblastoid cells, which was consistent with the participation of stromal elements in metastatic growth and with the microinjury hypothesis of metastasis.

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