CD147 and MMPs as key factors in physiological and pathological processes

Asgari, Rezvan; Vaisi-Raygani, Asad; Aleagha, Mohammad Sajad Emami; Mohammadi, Pantea; Bakhtiari, Mitra; Arghiani, Nahid

doi:10.1016/j.biopha.2022.113983

Cited by 28 publications

(14 citation statements)

References 143 publications

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“…Therefore, this hypoxic microenvironment can be capitalized to develop liver cancer‐selective targeted therapies. CD147 is a hub Ag that binds to other proteins (Intergrin, Hyaluronan, CD44, P‐gp/ABCB1, ABCG2, MCT‐1/4, CypA/B, and Gasdermin D) to drive the malignancy of cancer cells 2,3,5,14,26–28,34 . Previous studies revealed that hypoxia induces the upregulation of CD147 in liver cancer cells 35 .…”

Section: Discussionmentioning

confidence: 99%

“…CD147 is a hub Ag that binds to other proteins (Intergrin, Hyaluronan, CD44, P‐gp/ABCB1, ABCG2, MCT‐1/4, CypA/B, and Gasdermin D) to drive the malignancy of cancer cells. 2 , 3 , 5 , 14 , 26 , 27 , 28 , 34 Previous studies revealed that hypoxia induces the upregulation of CD147 in liver cancer cells. 35 Here, we found that hypoxia also increased CD147 expression on liver cancer cell surface (Figure S16 ).…”

Section: Discussionmentioning

confidence: 99%

“…This is largely attributed to the side effects such as rash, hemagglutination, and chills. 2 , 3 , 4 , 5 , 6 , 7 , 9 , 10 , 11 , 12 These side effects are derived from the residual low‐level expression of CD147 in some normal tissues, 3 , 13 , 14 standing out CD147‐targeting therapies are not spatially restricted to cancer tissue, and peripheral toxicity may reduce the therapeutic efficacy.…”

Section: Introductionmentioning

confidence: 99%

“…Once the azo‐bond was reduced under hypoxia, the reductive cleavage of azo groups yields a self‐immolative aminobenzyl carbamate that releases lysine and 4‐aminobenzyl alcohol, a byproduct with little cytotoxicity. 19 , 20 , 21 Upon recovery of intact structure initiated by the 1,6‐elimination reaction, 13 , 14 PEG 5000 is released, and conditional HAP18 Ab is allowed to specifically target CD147 on hypoxic cancer cells. Thus, eradicating the on‐target off‐tumor toxicity for liver cancer therapy (Figure 1 ).…”

Section: Introductionmentioning

confidence: 99%

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Hypoxia‐activated ADCC‐enhanced humanized anti‐CD147 antibody for liver cancer imaging and targeted therapy with improved selectivity

Qi,

Su,

Wang

et al. 2024

MedComm

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Therapeutic antibodies (Abs) improve the clinical outcome of cancer patients. However, on‐target off‐tumor toxicity limits Ab‐based therapeutics. Cluster of differentiation 147 (CD147) is a tumor‐associated membrane antigen overexpressed in cancer cells. Ab‐based drugs targeting CD147 have achieved inadequate clinical benefits for liver cancer due to side effects. Here, by using glycoengineering and hypoxia‐activation strategies, we developed a conditional Ab‐dependent cellular cytotoxicity (ADCC)‐enhanced humanized anti‐CD147 Ab, HcHAb18‐azo‐PEG5000 (HAP18). Afucosylated ADCC‐enhanced HcHAb18 Ab was produced by a fed‐batch cell culture system. Azobenzene (Azo)‐linked PEG5000 conjugation endowed HAP18 Ab with features of hypoxia‐responsive delivery and selective targeting. HAP18 Ab potently inhibits the migration, invasion, and matrix metalloproteinase secretion, triggers the cytotoxicity and apoptosis of cancer cells, and induces ADCC, complement‐dependent cytotoxicity, and Ab‐dependent cellular phagocytosis under hypoxia. In xenograft mouse models, HAP18 Ab selectively targets hypoxic liver cancer tissues but not normal organs or tissues, and has potent tumor‐inhibiting effects. HAP18 Ab caused negligible side effects and exhibited superior pharmacokinetics compared to those of parent HcHAb18 Ab. The hypoxia‐activated ADCC‐enhanced humanized HAP18 Ab safely confers therapeutic efficacy against liver cancer with improved selectivity. This study highlights that hypoxia activation is a promising strategy for improving the tumor targeting potential of anti‐CD147 Ab drugs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Hypoxia‐activated ADCC‐enhanced humanized anti‐CD147 antibody for liver cancer imaging and targeted therapy with improved selectivity

Qi,

Su,

Wang

et al. 2024

MedComm

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“…Basigin, also known as CD147 or extracellular MMP inducer (EMMPRIN), is a transmembrane glycoprotein belonging to the immunoglobulin superfamily that induces the synthesis of MMPs [ 241 ]. Serum soluble CD147 (sCD147) has been investigated to determine its possible role in SSc-related SRC pathogenesis.…”

Section: Other Molecules Markers Of Vascular Damagementioning

confidence: 99%

Current Trends in Vascular Biomarkers for Systemic Sclerosis: A Narrative Review

Fioretto

Rosa

Matucci‐Cerinic

et al. 2023

IJMS

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Systemic sclerosis (SSc, scleroderma) is a multifaceted rare connective tissue disease whose pathogenesis is dominated by immune dysregulation, small vessel vasculopathy, impaired angiogenesis, and both cutaneous and visceral fibrosis. Microvascular impairment represents the initial event of the disease, preceding fibrosis by months or years and accounting for the main disabling and/or life-threatening clinical manifestations, including telangiectasias, pitting scars, periungual microvascular abnormalities (e.g., giant capillaries, hemorrhages, avascular areas, ramified/bushy capillaries) clinically detectable by nailfold videocapillaroscopy, ischemic digital ulcers, pulmonary arterial hypertension, and scleroderma renal crisis. Despite a variety of available treatment options, treatment of SSc-related vascular disease remains problematic, even considering SSc etherogenity and the quite narrow therapeutic window. In this context, plenty of studies have highlighted the great usefulness in clinical practice of vascular biomarkers allowing clinicians to assess the evolution of the pathological process affecting the vessels, as well as to predict the prognosis and the response to therapy. The current narrative review provides an up-to-date overview of the main candidate vascular biomarkers that have been proposed for SSc, focusing on their main reported associations with characteristic clinical vascular features of the disease.

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Clinical glycoproteomics: methods and diseases

Wang,

Lei,

Zhao

et al. 2024

MedComm

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Glycoproteins, representing a significant proportion of posttranslational products, play pivotal roles in various biological processes, such as signal transduction and immune response. Abnormal glycosylation may lead to structural and functional changes of glycoprotein, which is closely related to the occurrence and development of various diseases. Consequently, exploring protein glycosylation can shed light on the mechanisms behind disease manifestation and pave the way for innovative diagnostic and therapeutic strategies. Nonetheless, the study of clinical glycoproteomics is fraught with challenges due to the low abundance and intricate structures of glycosylation. Recent advancements in mass spectrometry‐based clinical glycoproteomics have improved our ability to identify abnormal glycoproteins in clinical samples. In this review, we aim to provide a comprehensive overview of the foundational principles and recent advancements in clinical glycoproteomic methodologies and applications. Furthermore, we discussed the typical characteristics, underlying functions, and mechanisms of glycoproteins in various diseases, such as brain diseases, cardiovascular diseases, cancers, kidney diseases, and metabolic diseases. Additionally, we highlighted potential avenues for future development in clinical glycoproteomics. These insights provided in this review will enhance the comprehension of clinical glycoproteomic methods and diseases and promote the elucidation of pathogenesis and the discovery of novel diagnostic biomarkers and therapeutic targets.

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CD147 and MMPs as key factors in physiological and pathological processes

Cited by 28 publications

References 143 publications

Hypoxia‐activated ADCC‐enhanced humanized anti‐CD147 antibody for liver cancer imaging and targeted therapy with improved selectivity

Hypoxia‐activated ADCC‐enhanced humanized anti‐CD147 antibody for liver cancer imaging and targeted therapy with improved selectivity

Current Trends in Vascular Biomarkers for Systemic Sclerosis: A Narrative Review

Clinical glycoproteomics: methods and diseases

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