Case Study Recall Mr Jones

Recall Mr. Jones from the first case study. He was diagnosed with prostate cancer (PCa) at the age of 59. Mr. Jones is an average north American man, he is slightly overweight and easts a typical western diet high in saturated fats. Upon further discovery, it was observed that Mr. Jones had PCa with a Gleason score of 7 (4+3), and large regions of hypoxia surrounding the primary tumour. In a follow-up assessment with his oncologist, Mr. Jones underwent a computed tomography (CT) scan that did not show evidence of invasion beyond the prostate gland. Although the results of the CT scan boded well for Mr. Jones’ prognosis, the results do not definitively prove that the initial radical prostatectomy was successful in removing all of the PCa
Jones was in remission for about three years. During these three years he would have undergone an increased frequency of PSA monitoring as an extra precaution considering his intermediate risk classification. The remission during these three years may be attributed tumour cell dormancy. Tumour cell dormancy is a mechanism where metastic cells enter a quiescent state and become clinically undetectable in order to preserve their genetic material whilst in a microenvironment that does not support metastic growth. In the case of Mr. Jones, it is likely that metastasis and extravasation occurred prior to his remission period and radical prostatectomy. The exact classification of cell dormancy (angiogenic, immunogenic, or cellular dormancy) cannot be specified, but it can be hypothesized that cellular dormancy was the mechanism taking place during the three-year remission period. Considering that Mr. Jones’ PSA levels were undetectable for three years, it is likely that that the cancer cells were in a total quiescent state. Unlike the tumour cells in angiogenic dormancy and immunogenic dormancy that are still active but the rate of proliferation equals the rate of apoptosis or immune mediated apoptosis respectively, the cancer cells in cellular dormancy are completely inactive and would therefore produce no
Loss of cell-cell adhesion is one of the first mechanisms that must occur for metastasis to take place. During times of hypoxia, hypoxia inducible factor-1 (HIF-1) downregulates expression of E-cadherin, a cell-cell transmembrane adhesion protein that suppresses tissue invasion and metastasis. Decreased expression of E-cadherin gives tumour cells greater motility and a greater propensity to migrate towards the circulatory vasculature and lymphatics. After the loss of cell-cell adhesion, the loss of cell-matrix adhesion is required for successful metastasis. Normal cell-matrix adhesion is mediated by normal expression of integrins, but over expression of integrins α6 and β3 has been associated with increased tissue invasion specifically in PCa (Cress at al., 1995). Migration of motile cells through the extracellular matrix (ECM) requires proteolytic degradation of the ECM by matrix metalloproteinases (MMPs) and activation of the urokinase plasminogen activation system. MMPs are zinc-dependent endopeptidases that within healthy tissues are inhibited by tissue inhibitors of metalloproteinases (TIMPs), but within a pathophysiological state there is an increase in the MMPs:TIMPs ratio This imbalance in MMPs and TIMPs ratio is key to tumour motility, ECM degradation, and basement membrane degradation (Lokeshwar et al., 1993). Activation of plasmin, a component of the urokinase plasminogen activation system