Prostanoid induces premetastatic niche in regional lymph nodes

Ogawa, Fumihiro; Aoki, Hideki; Eshima, Koji; Yoshiya, Ikuto; Matsui, Yoshio; Hosono, Kanako; Kitasato, Hidero; Iyoda, Akira; Iwabuchi, Kazuya; Kumagai, Yoshito; Satoh, Yukitoshi; Narumiya, Shuh; Murakami, Masataka

doi:10.1172/jci73530

Cited by 72 publications

(66 citation statements)

References 63 publications

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“…[3][4][5][6][7][8][9][10][11][12][13][14] The original spatial distribution analysis used in the present study additionally highlighted that main lymphatic vascular modulations occur in the subcapsular sinus, the Figure 3. Association between the lymphatic vessel density (D2-40) and densities of CD8 C T lymphocytes, Foxp3 C T lymphocytes, CD20 C B lymphocytes and PD-1 C germinal centers in DLN¡ and SLN¡.…”

Section: Discussionmentioning

confidence: 61%

“…Previous experimental studies in animal models have highlighted a lymphovacular remodeling (lymphangiogenesis) in the first draining LN (sentinel LN or SLN) that occurs prior to metastasis. [3][4][5][6][7][8][9] So far, only a few clinical studies have documented pre-metastatic lymphovascular process in the SLN of patients with lung, breast and oral squamous carcinomas. [10][11][12][13][14] Moreover, the mechanisms underlying the pre-metastatic regulation remain unknown and its relationship with inflammation and immune responses is not documented.…”

Section: Introductionmentioning

confidence: 99%

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A specific immune and lymphatic profile characterizes the pre-metastatic state of the sentinel lymph node in patients with early cervical cancer

et al. 2017

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The lymph node (LN) pre-metastatic niche is faintly characterized in lymphophilic human neoplasia, although LN metastasis is considered as the strongest prognostic marker of patient survival. Due to its specific dissemination through a complex bilateral pelvic lymphatic system, early cervical cancer is a relevant candidate for investigating the early nodal metastatic process. In the present study, we analyzed in-depth both the lymphatic vasculature and the immune climate of pre-metastatic sentinel LN (SLN), in 48 cases of FIGO stage IB1 cervical neoplasms. An original digital image analysis methodology was used to objectively determine whole slide densities and spatial distributions of immunostained structures. We observed a marked increase in lymphatic vessel density (LVD) and a specific capsular and subcapsular distribution in pre-metastatic SLN when compared with non-sentinel counterparts. Such features persisted in the presence of nodal metastatic colonization. The inflammatory profile attested by CD8 C , Foxp3, CD20 and PD-1expression was also significantly increased in pre-metastatic SLN. Remarkably, the densities of CD20 C B cells and PD-1 expressing germinal centers were positively correlated with LVD. All together, these data strongly support the existence of a pre-metastatic dialog between the primary tumor and the first nodal relay. Both lymphatic and immune responses contribute to the elaboration of a specific premetastatic microenvironment in human SLN. Moreover, this work provides evidence that, in the context of early cervical cancer, a pre-metastatic lymphangiogenesis occurs within the SLN (pre-metastatic niche) and is associated with a specific humoral immune response.

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Section: Discussionmentioning

confidence: 61%

Section: Introductionmentioning

confidence: 99%

A specific immune and lymphatic profile characterizes the pre-metastatic state of the sentinel lymph node in patients with early cervical cancer

et al. 2017

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“…At distant metastatic sites, the arrival and successful colonization of tumor cells are often preceded by changes in the microenvironment of the metastatic organ—referred to as a premetastatic niche. Several studies have now elucidated some distinctive features of premetastatic lymph nodes, including increased lymphangiogenesis and lymph flow (122), remodeling of high endothelial venules (HEVs) (123–125), recruitment of myeloid cells, and reduction of effector lymphocyte numbers and function (Figure 5) (126). It is thought that lymph-transported molecules that originate from the primary tumor orchestrate these events as they arrive in the sentinel lymph node.…”

Section: Role Of the Lymphatic System In Cancer Progressionmentioning

confidence: 99%

“…CCL21 production is impaired (133), whereas Stat-3/S1PR1 signaling in myeloid cells (134) and prostaglandin E2 (PGE2) production in subcapsular sinus DCs are increased (126). Blocking Stat-3/S1PR1 reduces metastasis, whereas PGE2 production leads to SDF-1α production, which is known to attract CXCR4 + tumor cells and correlate with lymph node metastasis (135).…”

Section: Role Of the Lymphatic System In Cancer Progressionmentioning

confidence: 99%

The Lymphatic System in Disease Processes and Cancer Progression

Padera

Meijer

Munn

2016

Annu. Rev. Biomed. Eng.

184

141

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Advances in our understanding of the structure and function of the lymphatic system have made it possible to identify its role in a variety of disease processes. Because it is involved not only in fluid homeostasis but also in immune cell trafficking, the lymphatic system can mediate and ultimately alter immune responses. Our rapidly increasing knowledge of the molecular control of the lymphatic system will inevitably lead to new and effective therapies for patients with lymphatic dysfunction. In this review, we discuss the molecular and physiological control of lymphatic vessel function and explore how the lymphatic system contributes to many disease processes, including cancer and lymphedema.

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“…In this study, we examined the roles of the PG-generating enzyme COX-2 in the development of interstitial fibrosis in UUO models using the selective COX-2 inhibitor, celecoxib [8]. The accumulation of type I, III, and IV collagens in UUO kidneys was significantly increased in mice treated with celecoxib.…”

Section: Introductionmentioning

confidence: 99%