Cyclized Oligopeptide Targeting LRP5/6-DKK1 Interaction Reduces the Growth of Tumor Burden in a Multiple Myeloma Mouse Model

Park, Bo Mi; Kim, Eun Jin; Nam, Hee Jin; Zhang, Dongdong; Bae, Chu Hyun; Kang, Myeongmo; Kim, Heeyoun; Lee, Weontae; Bogen, Bjarne; Lim, Sung Kil

doi:10.3349/ymj.2017.58.3.505

Cited by 14 publications

(11 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, some innovative inhibitory strategies against DKK1 have been reported. Park et al generated a cyclic oligopeptide that could inhibit Wnt signaling pathway and reduce tumor burden in vivo (94). A fusion DNA vaccine composed of DKK1 and human HSP70 developed by Liu et al and a DKK1 DNA vaccine produced by Qian et al also consistently demonstrated therapeutic efficacies on murine multiple myeloma (70,71).…”

Section: Potential Role Of Dkk1 In Regulating Therapeutic Response Of Immune Checkpoint Inhibitorsmentioning

confidence: 99%

See 1 more Smart Citation

Dickkopf-1: A Promising Target for Cancer Immunotherapy

et al. 2021

View full text Add to dashboard Cite

Clinical studies in a range of cancers have detected elevated levels of the Wnt antagonist Dickkopf-1 (DKK1) in the serum or tumors of patients, and this was frequently associated with a poor prognosis. Our analysis of DKK1 gene profile using data from TCGA also proves the high expression of DKK1 in 14 types of cancers. Numerous preclinical studies have demonstrated the cancer-promoting effects of DKK1 in both in vitro cell models and in vivo animal models. Furthermore, DKK1 showed the ability to modulate immune cell activities as well as the immunosuppressive cancer microenvironment. Expression level of DKK1 is positively correlated with infiltrating levels of myeloid-derived suppressor cells (MDSCs) in 20 types of cancers, while negatively associated with CD8+ T cells in 4 of these 20 cancer types. Emerging experimental evidence indicates that DKK1 has been involved in T cell differentiation and induction of cancer evasion of immune surveillance by accumulating MDSCs. Consequently, DKK1 has become a promising target for cancer immunotherapy, and the mechanisms of DKK1 affecting cancers and immune cells have received great attention. This review introduces the rapidly growing body of literature revealing the cancer-promoting and immune regulatory activities of DKK1. In addition, this review also predicts that by understanding the interaction between different domains of DKK1 through computational modeling and functional studies, the underlying functional mechanism of DKK1 could be further elucidated, thus facilitating the development of anti-DKK1 drugs with more promising efficacy in cancer immunotherapy.

show abstract

Section: Potential Role Of Dkk1 In Regulating Therapeutic Response Of Immune Checkpoint Inhibitorsmentioning

confidence: 99%

“…Park et al. generated a cyclic oligopeptide that could inhibit Wnt signaling pathway and reduce tumor burden in vivo ( 94 ). A fusion DNA vaccine composed of DKK1 and human HSP70 developed by Liu et al.…”

Section: The Role Of Dkk1 In Modulating the Immune Cellsmentioning

confidence: 99%

Dickkopf-1: A Promising Target for Cancer Immunotherapy

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Moreover, suppressed osteoblast activity also results in a reduction of osteoblast-derived OPG, a decoy receptor for RANK-L. The reduction in osteoblast bone deposition and increase in osteoclast bone resorption lead to sustained bone destruction which promotes disease progression [ 186 ].…”

Section: The ‘Vicious Cycle’ Of Cancer Metastasis To Bonementioning

confidence: 99%

Cancer Metastases to Bone: Concepts, Mechanisms, and Interactions with Bone Osteoblasts

Shupp

Kolb

Mukhopadhyay

et al. 2018

Cancers

114

View full text Add to dashboard Cite

The skeleton is a unique structure capable of providing support for the body. Bone resorption and deposition are controlled in a tightly regulated balance between osteoblasts and osteoclasts with no net bone gain or loss. However, under conditions of disease, the balance between bone resorption and deposition is upset. Osteoblasts play an important role in bone homeostasis by depositing new bone osteoid into resorption pits. It is becoming increasingly evident that osteoblasts additionally play key roles in cancer cell dissemination to bone and subsequent metastasis. Our laboratory has evidence that when osteoblasts come into contact with disseminated breast cancer cells, the osteoblasts produce factors that initially reduce breast cancer cell proliferation, yet promote cancer cell survival in bone. Other laboratories have demonstrated that osteoblasts both directly and indirectly contribute to dormant cancer cell reactivation in bone. Moreover, we have demonstrated that osteoblasts undergo an inflammatory stress response in late stages of breast cancer, and produce inflammatory cytokines that are maintenance and survival factors for breast cancer cells and osteoclasts. Advances in understanding interactions between osteoblasts, osteoclasts, and bone metastatic cancer cells will aid in controlling and ultimately preventing cancer cell metastasis to bone.

show abstract

“…They developed a cyclic oligopeptide based on DKK1-LRP 5/6 interaction. 53 It inhibits the effect of DKK1 on osteoblast differentiation, and removes the inhibition of Wnt signaling pathway, thus reducing the tumor burden of MM. What's more, Liu et al have constructed human DKK1 and HSP70 fusion DNA vaccine (hDKK1-hhsp70).…”

Section: Role In Cancer Therapeuticsmentioning

confidence: 99%

<p>The Clinical Diagnostic and Prognostic Value of Dickkopf-1 in Cancer</p>

Li¹,

Gao²,

Yue³

2020

CMAR

View full text Add to dashboard Cite

The Wnt signaling pathway extensively participates in diverse processes such as embryonic development, maintenance of homeostasis and tumor pathogenesis. Dickkopf-1 (DKK1), a Wnt inhibitor, plays a vital role for over the past decades regarding its role in the regulation of several types of cancers. However, studies have shown that DKK1 is expressed differently in cancer and plays a role as a cancer-promoting factor or a tumor suppressor, which is worthy of further exploration. We herein study whether DKK1 is highly expressed in all cancers and plays a crucial role in promoting cancer. Furthermore, we discussed as to which stages of cancer development it plays in. Finally, the present detection methods were introduced and indicated the clinical application of DKK1 in tumor development.

show abstract

Cyclized Oligopeptide Targeting LRP5/6-DKK1 Interaction Reduces the Growth of Tumor Burden in a Multiple Myeloma Mouse Model

Cited by 14 publications

References 31 publications

Dickkopf-1: A Promising Target for Cancer Immunotherapy

Dickkopf-1: A Promising Target for Cancer Immunotherapy

Cancer Metastases to Bone: Concepts, Mechanisms, and Interactions with Bone Osteoblasts

<p>The Clinical Diagnostic and Prognostic Value of Dickkopf-1 in Cancer</p>

Contact Info

Product

Resources

About