[Cancer metastasis, genetic and microenvironmental factors of distant tissue: a review article]

Cancer is one of the main reasons of mortality worldwide, and more than 90 percent of cancer deaths are due to metastasis. Although primary tumors are curable using chemical adjuvant therapy or surgery, metastatic tumors are mostly incurable. This resistance shows the high rate of mortality among patients with metastatic disease. Being a sequential event, metastasis is a subtle and intricate process in which tumor cells undergo a plenty of changes and acquire the capacity of migration, invasion, survival and self-renewal which all are necessary for metastasis to happen. The key point in recognition and cure in invasive cancers is to identify critical genes, proteins and pathways involved, and show their relation with each other and the disease. Forming metastasis needs favorable genetic and microenvironmental elements of tumor cells and distant tissue, respectively. Unfavorable conditions in each steps of this process lead to arresting metastasis and subsequent dormancy, which is the most important phenomenon in relapse. In this review, benefiting from tens of reliable and recently identified data and personal experiences, it has been tried to draw new patterns associated with metastasis for further investigation. Determining genes, proteins and microenvironmental factors that affect metastasis, in a sequential manner, can help better understanding of this lethal process and subsequently a prosperous treatment

Differential WNT gene expression in various subtypes of acute lymphoblastic leukemia

Dysregulation of WNT signaling has been reported in many malignancies. This study was conducted to investigate the expression pattern of 14 members of the WNT gene family in different immunophenotypic subtypes of ALL. Semi-quantitative RT-PCR was performed on samples from 71 ALL patients and 36 age-matched healthy individuals. The ALL patients were categorized into B-ALL [76%], T-ALL [22.6%] and mixed lineage [1.4%] and the B-ALL cases were further classified into pro-B, pre-BI, pre-BII and immature/mature-B based on immunophenotypic results. Among the WNT genes, WNT-7B [p=0.026], WNT-9A [p=0.020] and WNT-16B [p=0.023] were significantly over-expressed, whereas WNT-2B [p=0.033], WNT-5A [p=0.016], WNT-7A [p<0.0001] and WNT-10A [p<0.0001] were down-regulated in B-ALL. Among the T-ALL subtype, however, significant down-regulation of WNT-2B, WNT-5B, WNT-7A, WNT-10A and WNT-11 was evident. Comparison between B-ALL subtypes showed significant over-expression of WNT-7B, WNT-9A and WNT-5B in certain subtypes. Our results suggest contribution of the WNT genes in leukemogenesis of ALL

Modeling breast acini in tissue culture for detection of malignant phenotype reversion to non-malignant phenotype

Evidence is accumulating to support disruption of tissue architecture as a powerful event in tumor formation. For the past four decades, intensive cancer research with the premise of "cancer as a cell based-disease" focused on finding oncogenes or tumor suppressor genes. However, the role of the tissue architecture was neglected. Three dimensional [3D] cell cultures which can recapitulate major aspects of the microenvironment are appropriate models for exploring cancer. For the first time in Iran, we have launched Matrigel based non-malignant, tumorigenic and reverted breast 3D cell cultures. Non-tumorigenic MCF-10A and tumorigenic MCF-7 breast cell lines were cultured on plastic and Matrigel. MCF-7 cell lines were reverted to normal phenotype via AIIB2 and LY 294002 inhibitors against beta1 integrin and class I phosphatidylinositol 3-kinase, respectively. MCF-10A acini were distinguishably different from MCF-7 on Matrigel. MCF-10A formed organized hollow spherical structures which were in stark contrast to the MCF-7 disorganized cluster of cells. Matrigel allowed visual monitoring of MCF-7 cells treated with inhibitors. After treatment of MCF-7 cells, we observed reversion of MCF-7 phenotype toward normal, comparable to MCF-10A acini. The 3D culture provides a microenvironment which allows malignant and non-malignant cells to demonstrate near physiological behavior and this can distinguish nonmalignant from malignant cells. The 3D culture also allows visual monitoring of malignant phenotype reversion to organized spheres