Research Projects

Extra cellular vesicles (EVs) are 30 nanometers (nm) to 10 micrometers (µm) lipid bilayer heterogenous vesicles that are released from all cell types starting from normal to cancerous [1]. The increasing evidence suggested that the exosome among the other EVs, can carry many biomolecules including proteins, mRNAs, miRNAs, and lipids that function as cell-cell communicator under normal and pathophysiological condition [2]. Compared to the normal cells, the cancer cells and irradiated cells release potentially large number of exosomes into extracellular matrix which contribute to the bystander’s effect, immunomodulation, development of radio-resistance, metastasis, angiogenesis, and formation of senescence [3, 4]. Being as a harbour of exclusive molecular and epigenetic components, the exosomes and modified exosome can be used for the theragnostic application in radiation bystander effect and development of radio-resistance, senescence in cancer cell during radiotherapy [5]. Squamous cell carcinoma (SCC) is one of the most common types of skin cancer. According to recent statistics from the Indian Cancer Society, it accounts for approximately 20% of all skin cancers diagnosed in India and second most common skin cancer in the USA [6]. A few sporadic reports are available, showing the involvement of exosomes in SCC [7-11]. But there is no detailed report available on how exosomal contents modulate the bystander’s effect of radiation, immunological pathways, radio-resistance, metastasis, angiogenesis, and senescence development in SCC. The identification of key exosomal factors involved, and their detailed mechanism of actions as the modifier of cellular signaling pathways are elusive. Along with the exosomal components, the role of cell free DNA (cfDNA) in modulating the radiation bystander effect and radiotherapy in SCC has not been studied yet. Previous literatures showed that the necrosis of the tumor cells after radiotherapy increases the amount of cfDNA in the circulating blood stream [12, 13]. The cfDNA/chromatin released from dying tumor cells can integrate into the genome of surrounding healthy cells to induce inflammation, death or oncogenic transformation [14]. However, the exact mechanism of releasing cfDNA and their mode of action have not been studied before. Additionally, the cfDNA released into media and blood, can be used to detect cancer stages and progression in radiotherapy [15]. Therefore, the present proposal has a broader aspect in terms of finding out the novel biomarkers (exosomal contents and cfDNA), and establishment of detailed mechanism of how exosome and cfDNA are involved in different radiation related modulations in SCC involving in vitro, in vivo and patients’ samples.