The effect of antagonizing RGD-binding integrin activity in papillary thyroid cancer cell lines

Abstract

Patients with papillary thyroid cancer (PTC) generally have good prognosis, but inoperable and radioactive iodine–refractory PTC still poses significant clinical challenges due to lack of effective treatment and higher mortality rates. Given the important role of integrins in multiple steps of tumor development, integrin-targeting therapy could be an effective strategy for PTC therapy. In this study, we investigated the antitumor effect of antagonizing Arg-Gly-Asp (RGD)-binding integrin activity in several PTC cell lines. Two RGD-binding integrin heterodimers αvβ3 and αvβ5 were first determined with fluorescence-activated cell sorting (FACS) and immunofluorescence assay. Cell proliferation and apoptosis were examined by Cell Counting Kit-8 assay and FACS, respectively. Cell migration and invasion were determined by transwell assays. All three PTC cell lines examined (BCPAP, K1, and TPC1) showed a moderate-to-high expression of αvβ3 and αvβ5 (P<0.05). Antagonizing the two heterodimers with the RGD-containing antagonist showed moderate inhibitory effect on cell viability of K1 and BCPAP cells, while the inhibitory effect was more significant in TPC1 cells. Similarly, the apoptotic effect induced by antagonizing αvβ3 and αvβ5 was much stronger in TPC1 cells than in BCPAP and K1 cells. Cell migration and invasion were significantly inhibited by αvβ3 and αvβ5 antagonism in all three PTC cell lines. Our results suggested that the demonstrated expression of RGD-binding integrin on PTC cells provides the possibility of integrin-targeting treatment in PTC. The strong apoptotic effect observed in TPC1 cells indicated that a subgroup of PTC patients may benefit from the cytotoxic effect of RGD-binding integrin antagonism, while the strong inhibitory effect on migration and invasion in all three PTC cells by antagonizing αvβ3 and αvβ5 showed there is an exciting possibility that targeting RGD-binding integrin may serve a potential therapeutic approach for metastatic PTC patients.

Clinical Value of 99mTc-3PRGD2 SPECT/CT in Differentiated Thyroid Carcinoma with Negative 131I Whole-Body Scan and Elevated Thyroglobulin Level

“…Using PET/CT in this group of patients is widely accepted, however, low sensitivity observed in patients with slightly increased sTg levels reflects that higher Tg level may be required to achieve a better FDG-PET accuracy 14 – 17 , 25 , 26 . Recent studies have suggested 99m Tc-3PRGD2 as a promising modality for guiding diagnosis and treatment of metastatic DTC lesions 22 , 27 . As far as we know, the present study is the first application of RGD imaging in detecting the possible recurrence or metastatic lesions in DTC patients with TENIS syndrome.…”

Theranostic Options for Radioiodine-Refractory Differentiated Thyroid Carcinoma: Recent Advances, Challenges, and Road Ahead

“…Consequently, integrin αvβ3 is overexpressed in the tumor vasculature of various malignancies, and is an attractive target for diagnostic and therapeutic applications. More interestingly, in thyroid cancer, the αvβ3 integrin is reported to be overexpressed on both the tumor endothelial cells as well as the tumor cell surface ( 26 , 27 ).…”

Other Positron Emission Tomography/Computed Tomography Tracers in Differential Thyroid Carcinoma ¡beyond the Use of 2-[18f]fdg

“…At present, studies have described the use of [ 68 Ga] Ga-NOTE-PRGD2 or [ 18 [22,24]; • Determine the presence of recurrent and/or distant disease in a patient with a diag nosis of TENIS syndrome [22]. A positive study [ 68 Ga] Ga-NOTE-PRGD2 or [ 18 F] AIF-NOTE-PRGD2 PET/CT can be used as a theragnostic agent to use treatmentbased on [ 177 Lu] Lu RGD or other chemotherapeutic agents such as paclitaxel and doxorubicin bound to RGD [22][23][24].…”