Hypoxia-regulated carbonic anhydrase IX (CAIX) protein is an independent prognostic indicator in triple negative breast cancer

Ong, Chong Hui Clara; Lee, Dong Yeul; Lee, Bernett; Li, Huihua; Lim, Jeffrey Chun Tatt; Lim, Jimmy; Yeong, Joe Poh Sheng; Lau, Hiu Yeung; Thike, Aye Aye; Tan, Puay Hoon; Iqbal, Jabed

doi:10.1186/s13058-022-01532-0

Cited by 26 publications

(16 citation statements)

References 47 publications

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“…Cancer cells often undergo metabolic reprogramming due to oxygen and nutrient deprivation within solid tumors, resulting in an upregulation of CAIX. Studies have shown that CAIX is a key hypoxia-inducible protein marker, and higher levels of CAIX are associated with poorer survival in patients with TNBC and ovarian, bladder, and lung cancers [ 45 , 46 ]. Additionally, the depletion of CAIX + cells has been shown to reduce the number of cancer stem cells (CSCs) in primary solid tumors and cancer cells in the bloodstream (CTCs) [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

Exploring the Role of Hypoxia-Inducible Carbonic Anhydrase IX (CAIX) in Circulating Tumor Cells (CTCs) of Breast Cancer

Twomey

Zhang

2023

Biomedicines

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Circulating tumor cells (CTCs) in the peripheral blood are believed to be the source of metastasis and can be used as a liquid biopsy to monitor cancer progression and therapeutic response. However, it has been challenging to accurately detect CTCs because of their low frequency and the heterogeneity of the population. In this study, we have developed an in vitro model of CTCs by using non-adherent suspension culture. We used this model to study a group of breast cancer cell lines with distinct molecular subtypes (TNBC, HER2+, and ER+/PR+). We found that, when these breast cancer cell lines lost their attachment to the extracellular matrix, they accumulated a subtype of cancer stem cells (CSC) that expressed the surface markers of stem cells (e.g., CD44+CD24−). These stem-like CTCs also showed high expressions of hypoxia-inducible gene products, particularly the hypoxia-inducible carbonic anhydrase IX (CAIX). Inhibition of CAIX activity was found to reduce CAIX expression and stem cell phenotypes in the targeted CTCs. Further studies are needed, using CTC samples from breast cancer patients, to determine the role of CAIX in CTC survival, CSC transition, and metastasis. CAIX may be a useful surface marker for the detection of CSCs in the blood, and a potential target for treating metastatic breast cancers.

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Section: Discussionmentioning

confidence: 99%

Exploring the Role of Hypoxia-Inducible Carbonic Anhydrase IX (CAIX) in Circulating Tumor Cells (CTCs) of Breast Cancer

Twomey

Zhang

2023

Biomedicines

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“…Multiple studies have shown a correlation between CAIX and poor prognosis or increased metastasis [ 74 , 75 ]. In thyroid cancer, patients with higher CAIX expression have a higher frequency of lymph node metastases [ 76 ].…”

Section: Hypoxic Secretomementioning

confidence: 99%

Role of the Hypoxic-Secretome in Seed and Soil Metastatic Preparation

Clemente-González

Carnero

2022

Cancers

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During tumor growth, the delivery of oxygen to cells is impaired due to aberrant or absent vasculature. This causes an adaptative response that activates the expression of genes that control several essential processes, such as glycolysis, neovascularization, immune suppression, and the cancer stemness phenotype, leading to increased metastasis and resistance to therapy. Hypoxic tumor cells also respond to an altered hypoxic microenvironment by secreting vesicles, factors, cytokines and nucleic acids that modify not only the immediate microenvironment but also organs at distant sites, allowing or facilitating the attachment and growth of tumor cells and contributing to metastasis. Hypoxia induces the release of molecules of different biochemical natures, either secreted or inside extracellular vesicles, and both tumor cells and stromal cells are involved in this process. The mechanisms by which these signals that can modify the premetastatic niche are sent from the primary tumor site include changes in the extracellular matrix, recruitment and activation of different stromal cells and immune or nonimmune cells, metabolic reprogramming, and molecular signaling network rewiring. In this review, we will discuss how hypoxia might alter the premetastatic niche through different signaling molecules.

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“…With the exception of renal cell carcinoma, CAIX expression is constitutively upregulated in and strongly correlated with reduced oxygenation status in primary and metastatic sites in several tumor types [15]. CAIX gene expression is associated with poor prognosis and is upregulated in LNMs of patients with breast and cervical cancer, oral cavity squamous cell carcinoma, melanoma, and as demonstrated by Tian et al in this issue of the European Journal of Nuclear Medicine and Molecular Imaging, in occult LNMs and ENEs of primary and recurrent nasopharyngeal carcinomas [15][16][17][18][19][20][21]. Thus, development of CAIX-specific diagnostic and therapeutic agents is emerging as a promising strategy to target hypoxic and metastatic lymph nodes.…”

mentioning

confidence: 92%