The growth and metastatic behavior of five human glioblastoma multiforme xenografts and nine human xenografts of various histological types were compared in severe combined immunodeficient (SCID) mice. The results demonstrate that the metastatic behavior of the human glioblastoma multiforme xenografts did not differ significantly from a variety of other histological xenografts when evaluated at the same transplantation site in the SCID model. These results are consistent with the hypothesis that the site of glioblastoma multiforme growth influences the extraneural metastatic spread of this disease and lead the authors to suggest that the clinical rarity of distant metastasis is not a fundamental property of these cells. A total of 340 male 7- to 8-week-old SCID mice received subcutaneous transplantation of tumor fragments (21-25 mice per tumor type). The tumor-bearing leg was amputated when the tumor reached a volume of 500 mm3; mice were observed for up to 5 months. There was a trend for a lower take rate, longer latent period, longer volume doubling time (VDT) and growth time (GT) in glioblastoma multiforme as opposed to carcinoma and soft tissue sarcoma xenografts. The highest local recurrence rates (78% and 68%) were observed in two glioblastomas multiforme. Both the glioblastoma multiforme and the other histological xenografts exhibited a widely varying metastatic rate: no correlation was demonstrated between VDT, GT, local control/recurrence, and distant metastasis. These findings show SCID mice to be an attractive model for further biological and preclinical studies of human glioblastoma multiforme.

No abstract

No abstract

Breast and prostate cancers preferentially metastasise to bone tissue, with metastatic lesions forming in the skeletons of most patients. On arriving in bone tissue, disseminated tumour cells enter a mechanical microenvironment that is substantially different to that of the primary tumour and is largely regulated by bone cells. Osteocytes, the most ubiquitous bone cell type, orchestrate healthy bone remodelling in response to physical exercise. However, the effects of mechanical loading of osteocytes on cancer cell behaviour is still poorly understood. The aim of this study was to characterise the effects of osteocyte mechanical stimulation on the behaviour of breast and prostate cancer cells. To replicate an osteocyte-controlled environment, this study treated breast (MDA-MB-231 and MCF-7) and prostate (PC-3 and LNCaP) cancer cell lines with conditioned media from MLO-Y4 osteocyte-like cells exposed to mechanical stimulation in the form of fluid shear stress. We found that osteocyte paracrine signalling acted to inhibit metastatic breast and prostate tumour growth, characterised by reduced proliferation and invasion and increased migration. In breast cancer cells, these effects were largely reversed by mechanical stimulation of osteocytes. In contrast, conditioned media from mechanically stimulated osteocytes had no effect on prostate cancer cells. To further investigate these interactions, we developed a microfluidic organ-chip model using the Emulate platform. This new organ-chip model enabled analysis of cancer cell migration, proliferation and invasion in the presence of mechanical stimulation of osteocytes by fluid shear stress, resulting in increased invasion of breast and prostate cancer cells. These findings demonstrate the importance of osteocytes and mechanical loading in regulating cancer cell behaviour and the need to incorporate these factors into predictive in vitro models of bone metastasis.

The absence of ACL function has been linked to abnormal kinematics and joint stability in patients with contemporary TKA. ACL-substituting implants could be a valuable treatment option capable of overcoming the limitations of contemporary TKA, particularly when retaining the native ACL is not feasible or is challenging.