What is the role of tumour-associated bone marrow derived cells in the therapeutic response of tumours?


Year:

Session type:

Muhammad Babur, Majid Ali, Brian Telfer, Kaye Williams

University of Manchester, Manchester, UK

Abstract

Background

Recent data suggests that bone-marrow derived cells (BMDC) can play an important role in tumour angiogenesis. BMDC can promote angiogenesis through direct incorporation into the tumour endothelium or via recruitment into peri-vascular sites. Their precise role in therapeutic response is yet to be established.

Aims

To establish a bone-marrow transplant (BMT) model to enable easy tracking of BMDC recruitment into tumours; to evaluate tumours implanted in to BMT mice; and to initiate studies into the effect of BMDC on tumour response to radiotherapy.

Results

EGFP-expressing C57/Bl-6 mice were used as donors in BMT experiments. The BMT procedure was optimised and tissue analysis undertaken to confirm successful engraftment. B16-F10 melanoma tumours were then initiated in BMT mice. Tumour growth following orthotopic skin implant was similar in BMT and wildtype mice. Metastatic progression was analysed in sub-sets of the B16-F10 tumours and again matched that observed in wildtype mice. Initial histological assessment of B16-F10 tumours established in BMT mice revealed the presence of BMDC identified by EGFP expression. Additional tumours were established and irradiated with fractionated radiotherapy. Tumours were excised at various time-points thereafter. The BMDC content of these tumours is currently being analysed. Identification of the cell populations recruited will be assessed using lineage specific markers (for example: endothelial, CD31, VEGFR1, VEGFR2; pericyte, 3G5; myeloid, CD11; CD45).

Conclusion

The BMT model has been successfully established and preliminary tumour studies undertaken. The ongoing analyses will substantiate the role of BMDC in tumour response to radiotherapy.

Background

Recent data suggests that bone-marrow derived cells (BMDC) can play an important role in tumour angiogenesis. BMDC can promote angiogenesis through direct incorporation into the tumour endothelium or via recruitment into peri-vascular sites. Their precise role in therapeutic response is yet to be established.

Aims

To establish a bone-marrow transplant (BMT) model to enable easy tracking of BMDC recruitment into tumours; to evaluate tumours implanted in to BMT mice; and to initiate studies into the effect of BMDC on tumour response to radiotherapy.

Results

EGFP-expressing C57/Bl-6 mice were used as donors in BMT experiments. The BMT procedure was optimised and tissue analysis undertaken to confirm successful engraftment. B16-F10 melanoma tumours were then initiated in BMT mice. Tumour growth following orthotopic skin implant was similar in BMT and wildtype mice. Metastatic progression was analysed in sub-sets of the B16-F10 tumours and again matched that observed in wildtype mice. Initial histological assessment of B16-F10 tumours established in BMT mice revealed the presence of BMDC identified by EGFP expression. Additional tumours were established and irradiated with fractionated radiotherapy. Tumours were excised at various time-points thereafter. The BMDC content of these tumours is currently being analysed. Identification of the cell populations recruited will be assessed using lineage specific markers (for example: endothelial, CD31, VEGFR1, VEGFR2; pericyte, 3G5; myeloid, CD11; CD45).

Conclusion

The BMT model has been successfully established and preliminary tumour studies undertaken. The ongoing analyses will substantiate the role of BMDC in tumour response to radiotherapy.