Targeting breast cancer‐initiating/stem cells with melanoma differentiation‐associated gene‐7/interleukin‐24. Issue 11 (6th July 2013)

• Record Type: Journal Article
• Authors: Bhutia, Sujit K.; Das, Swadesh K.; Azab, Belal; Menezes, Mitchell E.; Dent, Paul; Wang, Xiang‐Yang; Sarkar, Devanand; Fisher, Paul B.
• Is Part Of: International journal of cancer. Volume 133:Issue 11(2013:Dec. 01)
• Page Start: 2726
• Page End: 2736
• Publication Date: 2013-07-06
• Subjects: MDA‐7/IL‐24 -- apoptosis -- Wnt signaling -- cancer‐initiating/stem cells -- breast cancer; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.28289
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract : Melanoma differentiation‐associated gene‐7/interleukin‐24 ( mda ‐7/IL‐24) displays a broad range of antitumor properties including cancer‐specific induction of apoptosis, inhibition of tumor angiogenesis and modulation of antitumor immune responses. In our study, we elucidated the role of MDA‐7/IL‐24 in inhibiting growth of breast cancer‐initiating/stem cells. Ad. mda‐ 7 infection decreased proliferation of breast cancer‐initiating/stem cells without affecting normal breast stem cells. Ad. mda‐ 7 induced apoptosis and endoplasmic reticulum stress in breast cancer‐initiating/stem cells similar to unsorted breast cancer cells and inhibited the self‐renewal property of breast cancer‐initiating/stem cells by suppressing Wnt/β‐catenin signaling. Prevention of inhibition of Wnt signaling by LiCl increased cell survival upon Ad. mda ‐7 treatment, suggesting that Wnt signaling inhibition might play a key role in MDA‐7/IL‐24‐mediated death of breast cancer‐initiating/stem cells. In a nude mouse subcutaneous xenograft model, Ad .mda‐ 7 injection profoundly inhibited growth of tumors generated from breast cancer‐initiating/stem cells and also exerted a potent "bystander" activity inhibiting growth of distant uninjected tumors. Further studies revealed that tumor growth inhibition by Ad. mda‐ 7 was associated with a decrease in proliferation and angiogenesis, two intrinsic features of MDA‐7/IL‐24, and a reduction in vivo in the percentage of breast cancer‐initiating/stem cells. Our findings demonstrate that MDA‐7/IL‐24 is not only nontoxic to normal cells and normal stem cells but also can kill both unsorted cancer cells and enriched populations of cancer‐initiating/stem cells, providing further documentation that MDA‐7/IL‐24 might be a safe and effective way to eradicate cancers and also potentially establish disease‐free survival. Abstract : What's new? Cancer stem cells, or tumor‐initiating cells, are the small population of cells within a tumor that promote the growth and spread of the tumor. These self‐renewing cells produce high levels of proteins that thwart apoptosis, such as Bcl‐2, NF‐κB, and Akt. In this paper, the authors investigated a protein, MDA‐7/IL‐24, which has been shown to slow tumor growth and induce apoptosis. They found that it specifically targets the cancer stem cells and stops them from self‐renewing, which may help prevent recurrence of the disease.