Profilin 1 is a Potential Biomarker for Bladder Cancer Aggressiveness

Abstract

Of the most important clinical needs for bladder cancer (BC) management is the identification of biomarkers for disease aggressiveness. Urine is a "gold mine" for biomarker discovery, nevertheless, with multiple proteins being in low amounts, urine proteomics becomes challenging. In the present study we applied a fractionation strategy of urinary proteins based on the use of immobilized metal affinity chromatography for the discovery of biomarkers for aggressive BC. Urine samples from patients with non invasive (two pools) and invasive (two pools) BC were subjected to immobilized metal affinity chromatography fractionation and eluted Bladder cancer (BC) 1 is the second in incidence and mortality cancer of the genitourinary system (1) and estimated to be the ninth most common malignancy (2). It is associated with a high recurrence rate underscoring the need for continuous surveillance following initial treatment. Cystoscopy still remains the gold standard for diagnosis and follow-up monitoring of bladder cancer. However, it is an invasive and unpleasant procedure, rendering particularly the regular surveillance program (e.g. cystoscopy every three months for the first year following initial diagnosis) not well accepted by the patients (3, 4). Urine Cytology is a noninvasive current detection tool for BC, suffering however from suboptimal sensitivity, especially for low grade tumors and being subjected to interobserver variability (5). The invasive nature of cystoscopy and the low effectiveness of cytology have prompted the search for novel and better ways to diagnose the disease with special emphasis on the early detection of disease recurrences and/or progression.Urine is regularly used in clinical practice and yields a wealth of information about the state of an individual's health. Because it can be collected in a noninvasive way it is more accessible than plasma or serum. In addition, there is no need for trained personnel for urine collection. Urine contains cells and cellular debris, inorganic ions (K ϩ , Na ϩ , Cl Ϫ , and Ca ϩ2 ), organic molecules (urea, uric acid, and creatinine) and proteins. If renal function is normal, urinary protein content is less

Subcellular Localization and Ser-137 Phosphorylation Regulate Tumor-suppressive Activity of Profilin-1

“…Its expression is decreased in multiple types of carcinoma (breast, bladder, and pancreas) (10 -14), and its ectopic re-expression inhibits the proliferation and survival of several cancer cell lines in vitro and in vivo (12, 14 -16). Recently, low Pfn1 expression was correlated with poor outcome of bladder and pancreatic cancer patients (13,14). However, unlike classic tumor suppressor genes, homozygous deletion and somatic mutations of the PFN1 gene are extremely rare and have not been causally linked to cancer.…”

Molecular insights on context-specific role of profilin-1 in cell migration

“…[59][60][61][62] We surprisingly found that breast cancer cells and even normal human mammary epithelial cells (HMEC) display hypermotile phenotype when Pfn1 expression is suppressed, and conversely, overexpression of Pfn1 suppresses breast cancer cell motility. 25,63 Similar apparent inverse correlation between Pfn1 expression and tumor cell motility has also been documented for hepatocarcinoma cells.…”

Profilin 1 is essential for retention and metabolism of mouse hematopoietic stem cells in bone marrow

“…3,[5][6][7] By contrast, pfn1 decreases motility and invasiveness of breast cancer cells in a mouse model 8 and is down-regulated in invasive bladder cancer cells compared with noninvasive counterparts. 9 The in vivo role of pfn1 in tissue-specific stem cells has not been reported. The availability of the pfn1 flox/flox mice provided us an opportunity to clarify the function of pfn1 in different tissues and stem cells in the whole animal.…”