TSU68 Prevents Liver Metastasis of Colon Cancer Xenografts by Modulating the Premetastatic Niche

Yamamoto, Masayoshi; Kikuchi, Hirotoshi; Ohta, Michio; Kawabata, Toshiki; Hiramatsu, Yoshihiro; Kondo, Kenji; Baba, Megumi; Kamiya, Kinji; Tanaka, Tatsuo; Kitagawa, Masatoshi; Konno, Hiroyuki

doi:10.1158/0008-5472.can-08-1748

Cited by 94 publications

(76 citation statements)

References 39 publications

(48 reference statements)

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“…28, Figure 8C, and Supplemental Figure 7A). Not surprisingly, there was a significant overlap in up-and downregulated genes between pregnant mouse lungs and liver ( Figure 8D, Supplemental Figure 7B, and Supplemental Table 2), and several of the shared upregulated genes could be associated with infiltration of myeloid cells -possibly MDSCs.…”

Section: Gene Expression Profiles Of Pregnant and Virgin Mouse Lung Amentioning

confidence: 92%

Myeloid-derived suppressor cells are implicated in regulating permissiveness for tumor metastasis during mouse gestation

Mauti

Bitoux²,

Baumer³

et al. 2011

J. Clin. Invest.

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Metastasis depends on the ability of tumor cells to establish a relationship with the newly seeded tissue that is conducive to their survival and proliferation. However, the factors that render tissues permissive for metastatic tumor growth have yet to be fully elucidated. Breast tumors arising during pregnancy display early metastatic proclivity, raising the possibility that pregnancy may constitute a physiological condition of permissiveness for tumor dissemination. Here we have shown that during murine gestation, metastasis is enhanced regardless of tumor type, and that decreased NK cell activity is responsible for the observed increase in experimental metastasis. Gene expression changes in pregnant mouse lung and liver were shown to be similar to those detected in premetastatic sites and indicative of myeloid cell infiltration. Indeed, myeloid-derived suppressor cells (MDSCs) accumulated in pregnant mice and exerted an inhibitory effect on NK cell activity, providing a candidate mechanism for the enhanced metastatic tumor growth observed in gestant mice. Although the functions of MDSCs are not yet understood in the context of pregnancy, our observations suggest that they may represent a shared mechanism of immune suppression occurring during gestation and tumor growth.

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Section: Gene Expression Profiles Of Pregnant and Virgin Mouse Lung Amentioning

confidence: 92%

Myeloid-derived suppressor cells are implicated in regulating permissiveness for tumor metastasis during mouse gestation

Mauti

Bitoux²,

Baumer³

et al. 2011

J. Clin. Invest.

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“…In a nude mouse model of breast cancer, an increased infiltration of neutrophils increased invasiveness of the tumour, likely due to protease production (Yao et al 2007). In addition, the depletion of neutrophils in mouse models of fibrosarcoma and colon cancer significantly decreased metastasis in these animals (Tazawa et al 2003, Yamamoto et al 2008. The increase in neutrophil infiltration in endometrial adenocarcinoma induced by elevated chemokine expression has been described (Wallace et al 2009); however, the exact role that they are playing in endometrial adenocarcinoma is as yet unclear.…”

Section: Leukocytesmentioning

confidence: 96%

Inflammatory events in endometrial adenocarcinoma

Wallace

Gibson²,

Saunders

et al. 2010

Journal of Endocrinology

111

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Endometrial adenocarcinoma is the most common gynaecological malignancy in western countries. Many of the established risk factors for developing endometrial cancer are associated with excess exposure to oestrogen unopposed by progesterone. These include nulliparity, late onset of the menopause, post-menopausal hormone replacement therapy and obesity. However, a number of risk factors also promote inflammation, another feature proposed to influence cancer development. The human cycling endometrium undergoes regular and cyclical episodes of inflammation. Moreover, hormonal and genetic changes that occur early in the development of endometrial adenocarcinoma can exacerbate the local inflammatory environment. Via alterations in the expression of local mediators and immune cell function, these may contribute to the development of endometrial cancer. This review discusses the contribution of inflammation to the initiation and progression of endometrial adenocarcinoma. Manipulation of inflammatory pathways may therefore represent a therapeutic target in endometrial adenocarcinoma.

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“…Some promising achievements regarding translation of exosomerelated metastasis targets have been documented. TSU68, a small molecule inhibiting VEGFR1, PDGFRβ and FGFR1 has been shown to suppress CXCL1/CXCR2-dependent niche formation in the liver by inhibition of the inflammatory response through reduction of CXCL1 and IL12 (137). Furthermore, antibodies directed against αv on breast cancer cells prevented metastasis to other organs, but not to the lung (138,139,140).…”

Section: Translational Aspectsmentioning

confidence: 99%

The Multiple Roles of Exosomes in Metastasis

Weidle

Birzele

Kollmorgen

et al. 2017

CGP

168

133

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Abstract. Exosomes are important contributors to cellMetastases are responsible for the death of a large majority of cancer patients despite considerable progress in surgical techniques, radiotherapy, chemotherapy and targeted therapies including immuno-therapy (1). A dramatic reduction of metastatic burden has been observed, however, tumor elimination is almost always incomplete. This phenomenon is based on drug resistance, which is due to adaptation of intracellular pathways or on activation of survival-supporting autocrine and paracrine pathways and several secreted factors expressed by drug-sensitive tumor cells after therapy (2). Metastasis can occur through release of cancer cells from the primary tumor into body cavities that holds true for ovarian and CNS tumors, or via hematogeneous and lymphatic vessels of the circulatory system (3). Metastases of some tumors are directed besides to lymph nodes to mainly one type of organ only, such as prostate cancer to the bones, pancreatic cancer and uveal melanoma to the liver, whereas tumors such as melanoma, breast-and lung cancer can colonize several types of organs (3). Tumor cells have been found in the blood of patients with early-stage cancer and in some cases even before the primary tumor has been diagnosed (4, 5). Recently, making use of single-cell expression profiling, it has been shown that early metastatic cells possess a stem-like gene signature and give rise to heterogeneous metastases (6). The metastatic process is characterized by a defined sequence of events (7,8). Initial steps are detachment from the extracellular matrix (ECM), invasion into the surrounding tissue and proteolysis of the basement membrane. After intravasation, survival of circulating tumor cells (CTCs) is achieved by forming clusters, binding to platelets and immune evasion. Subsequently, they arrest in distal microvascular beds and extravasation can be achieved either by migration through intercellular junctions of endothelial cells (EC) or penetration of a single EC (9). CTCs can also colonize their tumors of origin, a process referred to as "tumor self-seeding", selecting for cancer cell populations more aggressive than those present in the primary tumor (10). After extravasation, colonization and outgrowth in the parenchyma of distant organs are the following steps. A common theme of the metastatic process is settlement of disseminated tumor cells (DTCs) into latency (dormancy), which can last from several months to decades (11). It has been observed that DTCs are recruited into pre-metastatic niches that support their survival by interactions with endothelial, myeloid cells, fibroblasts and other types of cells. After adaptation to the host microenvironment and suppression of an anti-tumoral immune response, DTCs are activated by not yet completely resolved mechanisms. Finally their outgrowth is based on an angiogenic switch mediated by pro-angiogenic factors and establishment of a vascular network to support the metabolic demands of colonizing tumor cells (12). In the follo...

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TSU68 Prevents Liver Metastasis of Colon Cancer Xenografts by Modulating the Premetastatic Niche

Cited by 94 publications

References 39 publications

Myeloid-derived suppressor cells are implicated in regulating permissiveness for tumor metastasis during mouse gestation

Myeloid-derived suppressor cells are implicated in regulating permissiveness for tumor metastasis during mouse gestation

Inflammatory events in endometrial adenocarcinoma

The Multiple Roles of Exosomes in Metastasis

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