Therapeutic Impact of Nanoparticle Therapy Targeting Tumor-Associated Macrophages

Penn, Courtney A.; Yang, Kun; Zong, Hong; Lim, Jae Young; Cole, Alex; Yang, Dongli; Baker, James R.; Goonewardena, Sascha N.; Buckanovich, Ronald J.

doi:10.1158/1535-7163.mct-17-0688

Cited by 52 publications

(41 citation statements)

References 46 publications

(60 reference statements)

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“…These findings establish a strong rationale for developing TAMs/CCL5 as a novel therapeutic target to inhibit PCSCs and prostate cancer metastasis. Penn et al also used to report that specific elimination of TAMs in murine models of ovarian cancer by TAMs-targeted nanoparticles could significantly decrease the CSCs population and therefore inhibit ovarian cancer growth 41 . Altogether, targeting TAMs may be a promising and powerful strategy to eliminate CSCs which deserves further investigations.…”

Section: Discussionmentioning

confidence: 99%

CCL5 derived from tumor-associated macrophages promotes prostate cancer stem cells and metastasis via activating β-catenin/STAT3 signaling

et al. 2020

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Prostate cancer stem cells (PCSCs) play a critical role in prostate cancer progression and metastasis, which remains an obstacle for successful prostate cancer treatment. Tumor-associated macrophages (TAMs) are the most abundant immune cell population within the tumor microenvironment (TME). Systematic investigation of the interaction and network signaling between PCSCs and TAMs may help in searching for the critical target to suppress PCSCs and metastasis. Herein, we demonstrated that TAMs-secreted CCL5 could significantly promote the migration, invasion, epithelial-mesenchymal transition (EMT) of prostate cancer cells as well as the self-renewal of PCSCs in vitro. QPCR screening validated STAT3 as the most significant response gene in prostate cancer cells following CCL5 treatment. RNA-sequencing and mechanistic explorations further revealed that CCL5 could promote PCSCs self-renewal and prostate cancer metastasis via activating the β-catenin/STAT3 signaling. Notably, CCL5 knockdown in TAMs not only significantly suppressed prostate cancer xenografts growth and bone metastasis but also inhibited the self-renewal and tumorigenicity of PCSCs in vivo. Finally, clinical investigations and bioinformatic analysis suggested that high CCL5 expression was significantly correlated with high Gleason grade, poor prognosis, metastasis as well as increased PCSCs activity in prostate cancer patients. Taken together, TAMs/CCL5 could promote PCSCs self-renewal and prostate cancer metastasis via activating β-catenin/STAT3 signaling. This study provides a novel rationale for developing TAMs/CCL5 as a potential molecular target for PCSCs elimination and metastatic prostate cancer prevention.

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Section: Discussionmentioning

confidence: 99%

CCL5 derived from tumor-associated macrophages promotes prostate cancer stem cells and metastasis via activating β-catenin/STAT3 signaling

et al. 2020

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“…In this concept, many approaches have been tested, including the common TIKs that are widely used, but the results are not that promising [91]. Nonetheless, Penn et al demonstrated that blockade of VEGF-C, which is secreted by TAMs, limited lymphagiogenesis and depleted TAMs [92]. As far as TANs are concerned, it was shown that they exert an anti-VEGF function.…”

Section: Mdsc Targeting For Cancer Therapymentioning

confidence: 99%

“…Specifically, Seeger et al showed that the presence of CD177 + neutrophils in colorectal cancer patients is associated with poor prognosis [93]. Finally, blocking of the Ang2/Tie axis was shown to reduce the tumor-promoting functions and recruitment of TAMs [92,94], and could be used as credentials denoting that blocking of secondary angiogenic mechanisms could improve anti-VEGF treatment [93].…”

Section: Mdsc Targeting For Cancer Therapymentioning

confidence: 99%

Myeloid-Derived Suppressor Cells: Major Figures that Shape the Immunosuppressive and Angiogenic Network in Cancer

Vetsika

Koukos

Κotsakis

2019

Cells

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Myeloid-derived suppressor cells (MDSCs) constitute a vast population of immature myeloid cells implicated in various conditions. Most notably, their role in cancer is of great complexity. They exert immunosuppressive functions like hampering cancer immunity mediated by T lymphocytes and natural killer cells, while simultaneously they can recruit T regulatory cells to further promote immunosuppression, thus shielding tumor cells against the immune defenses. In addition, they were shown to support tumor invasion and metastasis by inducing vascularization. Yet again, in order to exert their angiogenic activities, they do have at their disposal a variety of occasionally overlapping mechanisms, mainly driven by VEGF/JAK/STAT signaling. In this concept, they have risen to be a rather attractive target for therapies, including depletion or maturation, so as to overcome cancer immunity and suppress angiogenic activity. Even though, many studies have been conducted to better understand these cells, there is much to be done yet. This article hopes to shed some light on the paradoxal complexity of these cells, while elucidating some of the key features of MDSCs in relation to immunosuppression and, most importantly, to the vascularization processes, along with current therapeutic options in cancer, in relation to MDSC depletion.

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“…In addition to its role in maintaining organism homeostasis, the immune system also plays a crucial role in the modulation of ovarian function, as it regulates ovarian development, follicular maturation, ovulation and the formation of the corpus luteum [127][128][129][130][131]. In recent years, studies have also shown that immunosuppressive mechanisms and chronic inflammation play an important role in the pathogenesis of ovarian premature aging.…”

Section: Immunosuppressive Mechanisms and Chronic Inflammationmentioning

confidence: 99%

Mechanism for the Decision of Ovarian Surface Epithelial Stem Cells to Undergo Neo-Oogenesis or Ovarian Tumorigenesis

Zheng

Hong

et al. 2018

Cell Physiol Biochem

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The ovary is surrounded by a whitish layer of mesodermally derived ovarian surface epithelium (OSE) that lines the intraembryonic celom and comprises simple squamous to cuboidal to low pseudostratified columnar epithelial cells. Its integrity is maintained by simple desmosomes, incomplete tight junctions, several integrins and cadherins. Recent research has found that ovarian stem cells (OSCs) exist within the OSE and may be responsible for both neo-oogenesis and ovarian cancer during adult life. The factors determining whether OSCs undergo neo-oogenesis or ovarian cancer are of great interest to researchers and clinicians. Accumulating evidence suggests the mechanism for the decision of ovarian surface epithelial stem cells to undergo either neo-oogenesis or ovarian cancer transformation may comprise both internal and external factors. Here, we review recent progress on how the internal factors, including genes, signaling pathways and lncRNA: OSE stem cells mediate the development and progression of ovarian cancer through various genes such as p53, KRAS, BRAF, and PTEN, and mutations in PIK3CA, and through various signaling pathways, including TGF-B pathway, Wnt signaling pathway, Notch signaling pathway, NF-kB signal transducer and transcriptional activator 3 (STAT3) pathway and Hedghog (HH) pathway. A series of expressions of IncRNA have changed in epithelial ovarian cancer tissues and cell lines compared to normal ovarian tissues and cell lines. As well as external factors, including incessant ovulation, gonadotropin and chronicinflammation: Frequent ovulation, without long-term dormancy, increases the risk of illness, because repeated rupture and repair at the ovulation site provides an opportunity for the accumulation of genetic aberrations; FSH affects all aspects of ovarian cancer metastasis, such as inhibition of apoptosis, through Induction of increased expression of VEGFA (VEGF) to support tumor growth, promote vascular growth, and possibly alter certain oncogenic pathways, thereby promoting proliferation and invasive phenotypic inflammation contributes to tumorigenesis, which help determine whether OSCs undergo neo-oogenesis or ovarian tumorigenesis. Understanding this issue is critical for developing novel strategies for premature ovarian failure and ovarian cancer prevention and therapy.

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Therapeutic Impact of Nanoparticle Therapy Targeting Tumor-Associated Macrophages

Cited by 52 publications

References 46 publications

CCL5 derived from tumor-associated macrophages promotes prostate cancer stem cells and metastasis via activating β-catenin/STAT3 signaling

CCL5 derived from tumor-associated macrophages promotes prostate cancer stem cells and metastasis via activating β-catenin/STAT3 signaling

Myeloid-Derived Suppressor Cells: Major Figures that Shape the Immunosuppressive and Angiogenic Network in Cancer

Mechanism for the Decision of Ovarian Surface Epithelial Stem Cells to Undergo Neo-Oogenesis or Ovarian Tumorigenesis

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