Hypoxia and Hypoxia-Inducible Factors in Lymphedema

Tian, Wen; Kim, Dong-Eon; McQuiston, Alexander; Vinh, Ryan; Rockson, Stanley G.; Semenza, Gregg L.; Nicolls, Mark R.; Jiang, Xinguo

doi:10.3389/fphar.2022.851057

Cited by 5 publications

(3 citation statements)

References 121 publications

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“…Interestingly, Vcam1, Sele, and Pdpn could potentially associate with genes found in the cancer cell transcriptome, such as Itga4 and Lgal3bp [73][74][75]. Additionally, we identified other upregulated genes involved in angiogenesis, lymphangiogenesis, and LV remodeling, such as the vascular regulators Hif1a and Adm [66,67,76]. Moreover, we identified genes modulating angiogenesis and immunity, including Il6, Cxcl1, Cxcl2, Cxcl3, Cxcl4, and Cxcl5 [77-79] (Figure 3D), and genes involved in the broader regulation of soluble and immune cellular responses, such as the Ccl2, Ccl7, Ccl9, Ccl20, Csf1, Csf2, Csf3, Il23a, and Tnfsf15, receptor Il1r1, and the transcription factors Nfkb1, Nfkb2, Nfkbia, and Nfkbiz [31,80].…”

Section: Gene Expression Profiling Reveals a Reciprocal Regulation Of...mentioning

confidence: 84%

Lymph Vessels Associate with Cancer Stem Cells from Initiation to Malignant Stages of Squamous Cell Carcinoma

Cazzola,

Calzón Lozano,

Menne

et al. 2023

IJMS

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Tumor-associated lymph vessels and lymph node involvement are critical staging criteria in several cancers. In skin squamous cell carcinoma, lymph vessels play a role in cancer development and metastatic spread. However, their relationship with the cancer stem cell niche at early tumor stages remains unclear. To address this gap, we studied the lymph vessel localization at the cancer stem cell niche and observed an association from benign skin lesions to malignant stages of skin squamous cell carcinoma. By co-culturing lymphatic endothelial cells with cancer cell lines representing the initiation and promotion stages, and conducting RNA profiling, we observed a reciprocal induction of cell adhesion, immunity regulation, and vessel remodeling genes, suggesting dynamic interactions between lymphatic and cancer cells. Additionally, imaging analyses of the cultured cells revealed the establishment of heterotypic contacts between cancer cells and lymph endothelial cells, potentially contributing to the observed distribution and maintenance at the cancer stem cell niche, inducing downstream cellular responses. Our data provide evidence for an association of lymph vessels from the early stages of skin squamous cell carcinoma development, opening new avenues for better comprehending their involvement in cancer progression.

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Section: Gene Expression Profiling Reveals a Reciprocal Regulation Of...mentioning

confidence: 84%

Lymph Vessels Associate with Cancer Stem Cells from Initiation to Malignant Stages of Squamous Cell Carcinoma

Cazzola,

Calzón Lozano,

Menne

et al. 2023

IJMS

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“…Lymphatic vessels contract rhythmically, transporting lymph and inhibiting reflux by valves. When there is a problem with the lymphatic circulation, fluid accumulates in the interstitial space 17 . Recently, the incidence of lymphedema is increasing due to surgery and radiotherapy related to malignant neoplasms 11 , 16 .…”

Section: Discussionmentioning

confidence: 99%

Recellularized lymph node scaffolds with human adipose-derived stem cells enhance lymph node regeneration to improve lymphedema

Kang

Moon

Kim

et al. 2023

Sci Rep

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To overcome the limitations of lymphedema treatment, human adipose-derived stem cells (hADSCs) were injected into decellularized lymph nodes to produce a recellularized lymph node-scaffold, and the effect of lymphangiogenesis was investigated in lymphedema animal models. Axillary lymph nodes were harvested from Sprague Dawley rats (7 weeks old, 220–250 g) for decellularization. The decellularized lymph nodes were performed and PKH26-labeled hADSCs (1 × 106/50 µL) were injected in the decellularized lymph node-scaffolds. Forty rats were equally divided into four groups: lymphedema as control group, hADSC group, decellularized lymph node-scaffold group, and recellularized lymph node-scaffold group. The lymphedema model was made by removing inguinal lymph nodes, and hADSCs or scaffolds were transplanted. Histopathological assessments were performed by hematoxylin and eosin and Masson’s trichrome staining. Lymphangiogenesis was evaluated by Immunofluorescence staining and western blot. Decellularized lymph nodes showed virtually complete absence of cellular material and maintenance of lymph node architecture. The hADSCs were significantly observed in recellularized lymph node-scaffolds group. The recellularized lymph node-scaffold group was histologically similar to normal lymph nodes. The vascular endothelial growth factor A and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) in immunofluorescence staining were highly expressed in recellularized lymph node-scaffolds group. Also, the expression of LYVE-1 protein significantly increased in recellularized lymph node-scaffold group compared with others. Recellularized lymph node -scaffold had a much better therapeutic effect than stem cells or decellularized lymph node-scaffold alone, and induced stable lymphangiogenesis.

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“…For example, Hypoxia orchestrates the lymphovascular-immune ensemble in cancer [ 44 ]. Qigong exercise could safely and effectively help manage symptoms for those with, or at risk for, BCRL (breast cancer-related lymphedema) [ 49 ], primarily like through hypoxia-regulated pathways in lymphedema [ 50 ]. As such, Qigong-mediated hypoxia signaling pathways that could be utilized to reverse this imbalance and maximize the responses to targeted immunotherapies for patients with cancer is a manifestation of the mechanisms by which hypoxia-driven lymphatic remodeling and immunotolerance can be actively co-opted by CCs, tilting the immunological balance away or in favor of suppressive tumor and metastatic microenvironments.…”

Section: Perspectives Of Applications: Qigong Exercise Generates Oxyg...mentioning

confidence: 99%

Qigong Exercise Balances Oxygen Supply and Acid-Base to Modulate Hypoxia: A Perspective Platform toward Preemptive Health & Medicine

Zhang

2023

Medical Sciences

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Qigong is a meditative movement with therapeutic effects and is commonly practiced in Eastern medicine. A growing body of evidence validates its health benefits, leading to mechanistic questions about how it works. We propose a novel mechanism by which the “acid” caused by hypoxia affects metabolism, and the way it is neutralized through Qigong practice involves the body’s blood flow and vasculature modifications. Specifically, Qigong exercise generates an oxygen supply and acid-base balance against the hypoxic effects of underlying pathological conditions. We also propose that Qigong exercise mediated and focused on the local hypoxia environment of tissues might normalize the circulation of metabolic and inflammation accumulation in the tumor tissue and restore the normal metabolism of tissues and cells through calm, relaxation, and extreme Zen-style breathing that gravitates toward preemptive health and medicine. Thus, we propose the mechanisms of action related to Qigong, intending to unify Eastern and Western exercise theory.

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Hypoxia and Hypoxia-Inducible Factors in Lymphedema

Cited by 5 publications

References 121 publications

Lymph Vessels Associate with Cancer Stem Cells from Initiation to Malignant Stages of Squamous Cell Carcinoma

Lymph Vessels Associate with Cancer Stem Cells from Initiation to Malignant Stages of Squamous Cell Carcinoma

Recellularized lymph node scaffolds with human adipose-derived stem cells enhance lymph node regeneration to improve lymphedema

Qigong Exercise Balances Oxygen Supply and Acid-Base to Modulate Hypoxia: A Perspective Platform toward Preemptive Health & Medicine

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