Abstract
Simple SummaryThe treatment of oral squamous cell carcinoma (OSCC) represents a significant problem worldwide. Among cancers with the highest incidence, OSCC renders one of the worst prognoses. Therefore, novel prognostic biomarkers and therapeutic tools to tackle OSCC are urgently needed. Somatostatin-analogues (SSA) are an invaluable therapeutic option in the treatment of several cancers. We aimed to determine the expression levels of all somatostatin-receptors (SSTs) in OSCC, compared to adjacent healthy control tissues, to analyze the relationship of SSTs expression with key clinical and histopathological data, and to explore the direct in vitro effect of different SSAs on OSCC cancer cells. Our findings highlight a potential role of SST2 as a good prognostic biomarker for recurrence and metastasis in OSCC and unveil that SSA exerts antitumoral effects on OSCC cells, providing a relevant clinical conclusion, which should be soon tested for their use in humans.Oral squamous cell carcinoma (OSCC) incidence has increased by 50% over the last decade. Unfortunately, surgery and adjuvant radiotherapy and chemotherapy are still the mainstream modality of treatment, underscoring the need for alternative therapies. Somatostatin-analogues (SSA) are efficacious and safe treatments for a variety of tumors, but the presence of somatostatin-receptors (SSTs) and pharmacological effects of SSA on OSCC are poorly known. In this study, we demonstrated that SST2 and SST3 levels were significantly higher in OSCC, compared to adjacent healthy control tissues. SST2 expression was associated with less regional metastasis and a lower recurrence rate. Moreover, SST2 was elevated in OSCC and associated with histopathological good prognosis factors, such as high peritumoral inflammation, smaller depth of invasion, and expansive vs. infiltrative front of tumor invasion. Importantly, treatment with different SSA (octreotide, lanreotide, and pasireotide) significantly reduced cell-proliferation in OSCC primary cell cultures. Altogether, this study demonstrated that SST2 is overexpressed in OSCC vs. healthy tissues and could represent a novel prognostic biomarker, since its expression is associated with tumors that show better prognostic factors and less recurrent rate. Moreover, our data unveil clear antitumoral effects of SSAs on OSCC, opening new avenues to explore their potential as targeting therapy to OSCC.
Highlights
Oral squamous cell carcinoma (OSCC) continues to be an aggressive disease and a worldwide challenge [1]
This study includes the analysis of 37 patients diagnosed with OSCC, 19 men (52%) 3a. nRdes1u8ltws omen (48%), with a mean age of 64 ± 2-years-old
overall survival (OS) and Recurrence: Our analyses revealed that higher expression of SST2 was related to a lower rate of regional recurrence (p = 0.04) and both local and regional recurrence (p = 0.02) (Table 1)
Summary
Oral squamous cell carcinoma (OSCC) continues to be an aggressive disease and a worldwide challenge [1]. SST inhibitory actions are mediated through their so-called SST receptors (SSTs), which are widely distributed in normal and tumor tissues, and regulate, among other activities, cell proliferation, differentiation, and angiogenesis in many tumor types [11]. This property allows them to play a valuable role in tumor imaging (SST-scintigraphy or octreotide scan) [12]. In this sense, tumors cells typically express more than one SST-subtype, being the most frequently expressed SST2 subtype, and the most important target [13,14,15,16]. Synthetic SST analogues (SSAs) represent an attractive therapeutic target to treat the SST-positive tumor pathologies controlling hormone hypersecretion and tumor growth [17,18,19]
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