The Lymphatic System in Disease Processes and Cancer Progression

Padera, Timothy P.; Meijer, Eelco F. J.; Munn, Lance L.

doi:10.1146/annurev-bioeng-112315-031200

Cited by 196 publications

(153 citation statements)

References 247 publications

(317 reference statements)

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“…They have weaker interendothelial junctions and more “transendothelial channels”—vesiculo–vascular organelles—structural substrates of increased vessel leakiness (Goel et al 2011). Lymphatic ECs line the luminal surface of lymphatic vessels, which drain excess fluid from tissues (Alitalo 2011; Kesler et al 2013; Padera et al 2016). In tumors, normal cell-surface markers of lymphatic ECs are expressed in both blood and lymphatic vessels, underscoring the abnormality of these cells (Padera et al 2002; Jain 2014).…”

Section: Tumor Microenvironmentmentioning

confidence: 99%

Reengineering the Tumor Microenvironment to Alleviate Hypoxia and Overcome Cancer Heterogeneity

Martin

Fukumura

Duda

et al. 2016

Cold Spring Harb Perspect Med

132

117

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Solid tumors consist of cancer cells and stromal cells, including resident and transiting immune cells—all ensconced in an extracellular matrix (ECM)—nourished by blood vessels and drained by lymphatic vessels. The microenvironment constituents are abnormal and heterogeneous in morphology, phenotype, and physiology. Such irregularities include an inefficient tumor vascular network comprised of leaky and compressed vessels, which impair blood flow and oxygen delivery. Low oxygenation in certain tumor regions—or focal hypoxia—is a mediator of cancer progression, metastasis, immunosuppression, and treatment resistance. Thus, repairing an abnormal and heterogeneous microenvironment—and hypoxia in particular—can significantly improve treatments of solid tumors. Here, we summarize two strategies to reengineer the tumor microenvironment (TME)—vessel normalization and decompression—that can alleviate hypoxia. In addition, we discuss how these two strategies alone and in combination with each other—or other therapeutic strategies—may overcome the challenges posed by cancer heterogeneity.

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Section: Tumor Microenvironmentmentioning

confidence: 99%

Reengineering the Tumor Microenvironment to Alleviate Hypoxia and Overcome Cancer Heterogeneity

Martin

Fukumura

Duda

et al. 2016

Cold Spring Harb Perspect Med

132

117

View full text Add to dashboard Cite

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“…When the metastatic tumor enters a novel environment, CD4 + and CD8 + T cells may help them to evade the host immune system 144, 145. The remodeling of unusual endothelial venules (HEVs) can indirectly influence immune cells to traffic into lymph nodes 146. Though some immune cells traffic into the lymph nodes through the draining afferent lymphatic vessels, lymphocyte recruitment into the SLN via HEVs is fundamental 144.…”

Section: The Blood and Lymphatic Vascular Networkmentioning

confidence: 99%

Role of tumor microenvironment in tumorigenesis

et al. 2017

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Tumorigenesis is a complex and dynamic process, consisting of three stages: initiation, progression, and metastasis. Tumors are encircled by extracellular matrix (ECM) and stromal cells, and the physiological state of the tumor microenvironment (TME) is closely connected to every step of tumorigenesis. Evidence suggests that the vital components of the TME are fibroblasts and myofibroblasts, neuroendocrine cells, adipose cells, immune and inflammatory cells, the blood and lymphatic vascular networks, and ECM. This manuscript, based on the current studies of the TME, offers a more comprehensive overview of the primary functions of each component of the TME in cancer initiation, progression, and invasion. The manuscript also includes primary therapeutic targeting markers for each player, which may be helpful in treating tumors.

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“…In addition, aberrant levels of lymphangiogenesis are common in numerous primary human cancers including melanoma, breast, lung, and head and neck . Furthermore, increased lymphangiogenesis, particularly at the margins of primary tumors, is strongly implicated in metastasis through the lymphatic vasculature . Elevated expression of VEGF‐C and VEGF‐D by cancer cells is also correlated with poor prognosis, invasion, and metastasis .…”

Section: Microfluidic Approaches For Studying Lymphatic Vasculaturementioning

confidence: 99%

Application of microscale culture technologies for studying lymphatic vessel biology

2019

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Immense progress in microscale engineering technologies has significantly expanded the capabilities of in vitro cell culture systems for reconstituting physiological microenvironments that are mediated by biomolecular gradients, fluid transport, and mechanical forces. Here, we examine the innovative approaches based on microfabricated vessels for studying lymphatic biology. To help understand the necessary design requirements for microfluidic models, we first summarize lymphatic vessel structure and function. Next, we provide an overview of the molecular and biomechanical mediators of lymphatic vessel function. Then we discuss the past achievements and new opportunities for microfluidic culture models to a broad range of applications pertaining to lymphatic vessel physiology. We emphasize the unique attributes of microfluidic systems that enable the recapitulation of multiple physicochemical cues in vitro for studying lymphatic pathophysiology. Current challenges and future outlooks of microscale technology for studying lymphatics are also discussed. Collectively, we make the assertion that further progress in the development of microscale models will continue to enrich our mechanistic understanding of lymphatic biology and physiology to help realize the promise of the lymphatic vasculature as a therapeutic target for a broad spectrum of diseases.

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The Lymphatic System in Disease Processes and Cancer Progression

Cited by 196 publications

References 247 publications

Reengineering the Tumor Microenvironment to Alleviate Hypoxia and Overcome Cancer Heterogeneity

Reengineering the Tumor Microenvironment to Alleviate Hypoxia and Overcome Cancer Heterogeneity

Role of tumor microenvironment in tumorigenesis

Application of microscale culture technologies for studying lymphatic vessel biology

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