PDGF beta targeting in cervical cancer cells suggest a fine-tuning of compensatory signalling pathways to sustain tumourigenic stimulation.

The platelet-derived growth factor (PDGF) signalling pathway has been reported to play an important role in human cancers by modulating autocrine and paracrine processes such as tumour growth, metastasis and angiogenesis. Several clinical trials document the benefits of targeting this pathway; however, in cervical cancer the role of PDGF signalling in still unclear. In this study, we used siRNA against PDGF beta (PDGFBB) to investigate the cellular and molecular mechanisms of PDGFBB signalling in Ca Ski and HeLa cervical cancer cells. Our results show that PDGFBB inhibition in Ca Ski cells led to rapid alterations of the transcriptional pattern of 579 genes, genes that are known to have antagonistic roles in regulating tumour progression. Concomitantly, with the lack of significant effects on cervical cancer cells proliferation, apoptosis, migration or invasion, these findings suggests that cervical cancer cells shift between compensatory signalling pathways to maintain their behaviour. The observed autocrine effects were limited to cervical cancer cells ability to adhere to an endothelial cell (EC) monolayer. However, by inhibiting PDGFBB on cervical cells, we achieved reduced proliferation of ECs in co-culture settings and cellular aggregation in conditioned media. Because of lack of PDGF receptor expression on ECs, we believe that these effects are a result of indirect PDGFBB paracrine signalling mechanisms. Our results shed some light into the understanding of PDGFBB signalling mechanism in cervical cancer cells, which could be further exploited for the development of synergistic anti-tumour and anti-angiogenic therapeutic strategies.

Breast cancer stem-like cells: clinical implications and therapeutic strategies.

Breast cancer is the most frequently diagnosed cancer in women, being also the leading cause of cancer death among female population, including in Romania. Resistance to therapy represents a major problem for cancer treatment. Current cancer treatments are both expensive and induce serious side effects; therefore ineffective therapies are both traumatic and pricy. Characterizing predictive markers that can identify high-risk patients could contribute to dedicated/personalized therapy to improve the life quality and expectancy of cancer patients. Moreover, there are some markers that govern specific tumor molecular features that can be targeted with specific therapies for those patients who are most likely to benefit. The identification of stem cells in both normal and malignant breast tissue have lead to the hypothesis that breast tumors arise from breast cancer stem-like cells (CSCs), and that these cells influence tumor's response to therapy. CSCs have similar self-renewal properties to normal stem cells, however the balance between the signaling pathways is altered towards tumor formation In this review, we discuss the molecular aspects of breast CSCs and the controversies regarding their use in the diagnosis and treatment decision of breast cancer patients.