The most effective but largely ignored target for prostate cancer early detection and intervention

Abstract

Over the past two decades, the global efforts for the early detection and intervention of prostate cancer seem to have made significant progresses in the basic researches, but the clinic outcomes have been disappointing: (1) prostate cancer is still the most common non-cutaneous cancer in Europe in men, (2) the age-standardized prostate cancer rate has increased in nearly all Asian and African countries, (3) the proportion of advanced cancers at the diagnosis has increased to 8.2% from 3.9% in the USA, (4) the worldwide use of PSA testing and digital rectal examination have failed to reduce the prostate cancer mortality, and (5) there is still no effective preventive method to significantly reduce the development, invasion, and metastasis of prostate cancer… Together, these facts strongly suggest that the global efforts during the past appear to be not in a correlated target with markedly inconsistent basic research and clinic outcomes. The most likely cause for the inconsistence appears due to the fact that basic scientific studies are traditionally conducted on the cell lines and animal models, where it is impossible to completely reflect or replicate the in vivo status. Thus, we would like to propose the human prostate basal cell layer (PBCL) as “the most effective target for the early detection and intervention of prostate cancer”. Our proposal is based on the morphologic, immunohistochemical and molecular evidence from our recent studies of normal and cancerous human prostate tissues with detailed clinic follow-up data. We believe that the human tissue-derived basic research data may provide a more realistic roadmap to guide the clinic practice and to avoid the potential misleading from in vitro and animal studies.

The most likely but largely ignored triggering factor for breast (or all) cancer invasion

“…Tenascin C is an extracellular matrix glycoprotein, which paves the paths and facilitates the migration and metastasis of breast cancer cells 117 - 119 . Our previous studies have shown that Tenascin C is also highly expressed at distinct degenerating prostate basal cells, and EP cells in the vicinity of areas with elevated Tenascin C often lose the cohesion 120 - 125 (Figure 13 ).…”

“…Our hypothesis is very likely to be applicable to the invasion cascade observed in all EP-derived malignancies. Our previous studies of human prostate, lung, gastric, colorectal, skin, salivary gland, and cervical tumor tissues have consistently seen that the capsules of these tissues (especially the prostate tumor) harbor morphologically and immunohistochemically similar focal disruptions, which are associated with EP cell alterations that are essentially identical as those seen in the breast [109,110,[120][121][122][123][124][125].…”

Molecular Anatomy of Prostate Cancer and Its Implications in Active Surveillance and Early Intervention Strategies

“…Positioned beneath the basal layer and separated by a basement membrane [51], the non-epithelial prostate microenvironment, collectively termed 'stroma', is composed of various cell types. The stroma is a complex cellular network that plays a vital role for normal prostate development and related diseases [52][53][54][55].…”

ALKBH5 Suppresses Autophagy in Prostate Cancer Cells via Inhibiting m6A-Modification of TSPAN1 mRNA

“…Autophagy is associated with multiple biological processes in PCa, and studies have shown that autophagy can promote the invasion and progression of PCa and simultaneously resist radiation-induced damage [6,8,9]. The cooperative effects of multiple cancer suppressor genes and oncogenes are involved in the development and metastasis of PCa [10,11].…”