Chinmayee Sethy1, Kunal Goutam2, Deepika Nayak1, Rajalaxmi Pradhan1, Sefinew Molla1, Subhajit Chatterjee1, Niranjan Rout3, Michael D Wyatt4, Satya Narayan5, Chanakya Nath Kundu6. 1. Cancer Biology Division, KIIT School of Biotechnology, Kalinga Institute of Industrial Technology, Campus-11, Patia, Bhubaneswar, 751024, Odisha, India. 2. Department of Surgical Oncology, Acharya Harihar Regional Cancer Centre, Cuttack, 753007, Odisha, India. 3. Department of Oncopathology, Acharya Harihar Regional Cancer Centre, Cuttack, 753007, Odisha, India. 4. Department of Drug Discovery and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC, USA. 5. Department of Anatomy and Cell Biology, College of Medicine, University of Florida, Gainesville, FL, 32610, USA. 6. Cancer Biology Division, KIIT School of Biotechnology, Kalinga Institute of Industrial Technology, Campus-11, Patia, Bhubaneswar, 751024, Odisha, India. cnkundu@gmail.com.
Abstract
PURPOSE: In the present study, we have systematically examined the clinical significance of Nectin-4 (encoded by the PVRL-4 gene), a marker for breast cancer stem cells (CSCs), in cancer metastasis and angiogenesis using a variety of human specimens, including invasive duct carcinoma (IDC) with multiple grades, several types of primary tumors to local and distant relapses, lymph node metastases and circulating tumor cells (CTCs). METHODS: Nectin-4 was overexpressed in more than 92% of samples with 65.2% Nectin-4-positive cells. The level of expression was increased with increasing tumor grade (GI-III) and size (T1-4) of IDC specimens. RESULTS: More induction of Nectin-4 was noted in relapsed samples from a variety of tumors (colon, tongue, liver, kidney, ovary, buccal mucosa) in comparison to primary tumors, while paired adjacent normal tissues do not express any Nectin-4. A high expression of Nectin-4 along with other representative markers in CTCs and lymph node metastasis was also observed in cancer specimens. An increased level of Nectin-4 along with representative metastatic (CD-44, Sca1, ALDH1, Nanog) and angiogenic (Ang-I, Ang-II, VEGF) markers were noted in metastatic tumors (local and distant) in comparison to primary tumors that were correlated with different grades of tumor progression. In addition, greater expression of Nectin-4 was observed in secondary tumors (distant metastasis, e.g., breast to liver or stomach to gall bladder) in comparison to primary tumors. CONCLUSION: Our study demonstrated a significant correlation between Nectin-4 expression and tumor grade as well as stages (p < 0.001), suggesting its association with tumor progression. Nectin-4 was overexpressed at all stages of metastasis and angiogenesis, thus appearing to play a major role in tumor relapse through the PI3K-Akt-NFκβ pathway.
PURPOSE: In the present study, we have systematically examined the clinical significance of Nectin-4 (encoded by the PVRL-4 gene), a marker for breast cancer stem cells (CSCs), in cancer metastasis and angiogenesis using a variety of human specimens, including invasive duct carcinoma (IDC) with multiple grades, several types of primary tumors to local and distant relapses, lymph node metastases and circulating tumor cells (CTCs). METHODS:Nectin-4 was overexpressed in more than 92% of samples with 65.2% Nectin-4-positive cells. The level of expression was increased with increasing tumor grade (GI-III) and size (T1-4) of IDC specimens. RESULTS: More induction of Nectin-4 was noted in relapsed samples from a variety of tumors (colon, tongue, liver, kidney, ovary, buccal mucosa) in comparison to primary tumors, while paired adjacent normal tissues do not express any Nectin-4. A high expression of Nectin-4 along with other representative markers in CTCs and lymph node metastasis was also observed in cancer specimens. An increased level of Nectin-4 along with representative metastatic (CD-44, Sca1, ALDH1, Nanog) and angiogenic (Ang-I, Ang-II, VEGF) markers were noted in metastatic tumors (local and distant) in comparison to primary tumors that were correlated with different grades of tumor progression. In addition, greater expression of Nectin-4 was observed in secondary tumors (distant metastasis, e.g., breast to liver or stomach to gall bladder) in comparison to primary tumors. CONCLUSION: Our study demonstrated a significant correlation between Nectin-4 expression and tumor grade as well as stages (p < 0.001), suggesting its association with tumor progression. Nectin-4 was overexpressed at all stages of metastasis and angiogenesis, thus appearing to play a major role in tumor relapse through the PI3K-Akt-NFκβ pathway.
Entities:
Keywords:
Angiogenesis; Cancer relapse; Circulating tumor cells; Metastasis; Nectin-4
Authors: Kristin L M Boylan; Petra C Buchanan; Rory D Manion; Dip M Shukla; Kelly Braumberger; Cody Bruggemeyer; Amy P N Skubitz Journal: Oncotarget Date: 2017-02-07
Authors: Monica Benvenuto; Laura Masuelli; Enrico De Smaele; Massimo Fantini; Rosanna Mattera; Danilo Cucchi; Elena Bonanno; Enrica Di Stefano; Giovanni Vanni Frajese; Augusto Orlandi; Isabella Screpanti; Alberto Gulino; Andrea Modesti; Roberto Bei Journal: Oncotarget Date: 2016-02-23