Cancer Salivary Biomarkers for Tumours Distant to the Oral Cavity

Rapado‐González, Óscar; Majem, Blanca; Muinelo‐Romay, Laura; López‐López, Rafael; Suárez‐Cunqueiro, María Mercedes

doi:10.3390/ijms17091531

Cited by 29 publications

(22 citation statements)

References 87 publications

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“…Liquid biopsies are considered as a non-invasive alternative to tissue biopsies and can provide advanced diagnostic information from a small amount of body fluid such as blood. Notably, liquid biopsy has attracted attention as an important technique for early detection and diagnosis of cancer and various pathological conditions [157] by using blood [158,159], saliva [160,161,162], urine [163,164,165], stool [166,167], semen, sweat, tear, nasal mucus, breast milk, cerebrospinal fluid, amniotic fluid, and malignant ascites [168,169,170,171] (Figure 3).…”

Section: Hsps As Biomarkers Detectable By Liquid Biopsiesmentioning

confidence: 99%

Roles of Extracellular HSPs as Biomarkers in Immune Surveillance and Immune Evasion

Taha

Ono

Eguchi

2019

IJMS

143

139

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Extracellular heat shock proteins (ex-HSPs) have been found in exosomes, oncosomes, membrane surfaces, as well as free HSP in cancer and various pathological conditions, also known as alarmins. Such ex-HSPs include HSP90 (α, β, Gp96, Trap1), HSP70, and large and small HSPs. Production of HSPs is coordinately induced by heat shock factor 1 (HSF1) and hypoxia-inducible factor 1 (HIF-1), while matrix metalloproteinase 3 (MMP-3) and heterochromatin protein 1 are novel inducers of HSPs. Oncosomes released by tumor cells are a major aspect of the resistance-associated secretory phenotype (RASP) by which immune evasion can be established. The concepts of RASP are: (i) releases of ex-HSP and HSP-rich oncosomes are essential in RASP, by which molecular co-transfer of HSPs with oncogenic factors to recipient cells can promote cancer progression and resistance against stresses such as hypoxia, radiation, drugs, and immune systems; (ii) RASP of tumor cells can eject anticancer drugs, targeted therapeutics, and immune checkpoint inhibitors with oncosomes; (iii) cytotoxic lipids can be also released from tumor cells as RASP. ex-HSP and membrane-surface HSP (mHSP) play immunostimulatory roles recognized by CD91+ scavenger receptor expressed by endothelial cells-1 (SREC-1)+ Toll-like receptors (TLRs)+ antigen-presenting cells, leading to antigen cross-presentation and T cell cross-priming, as well as by CD94+ natural killer cells, leading to tumor cytolysis. On the other hand, ex-HSP/CD91 signaling in cancer cells promotes cancer progression. HSPs in body fluids are potential biomarkers detectable by liquid biopsies in cancers and tissue-damaged diseases. HSP-based vaccines, inhibitors, and RNAi therapeutics are also reviewed.

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Section: Hsps As Biomarkers Detectable By Liquid Biopsiesmentioning

confidence: 99%

Roles of Extracellular HSPs as Biomarkers in Immune Surveillance and Immune Evasion

Taha

Ono

Eguchi

2019

IJMS

143

139

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“…22 Similarly, mass spectrometry (MS)-based analysis with two-dimensional gel electrophoresis and Affymetrix HG-U133-Plus-2.0 Array have also been extensively used for early detection of different cancers such as lung, gastric, breast, and pancreatic cancers. 23 Historically, blood has been the primary diagnostic body fluid for analyzing changes in analyte concentration as an indicator of pathophysiological state. However, due to its noninvasive and ease of collection method, saliva has gained momentum as a body fluid that can be used to identify protein markers for a number of diseases, both local (eg, oral, periodontal disease 24 and primary Sjögren's syndrome 25 ) and systemic, including breast and ovarian cancers.…”

mentioning

confidence: 99%

“…However, due to its noninvasive and ease of collection method, saliva has gained momentum as a body fluid that can be used to identify protein markers for a number of diseases, both local (eg, oral, periodontal disease 24 and primary Sjögren's syndrome 25 ) and systemic, including breast and ovarian cancers. 23 In fact, women with systemic diseases, such as breast and ovarian cancers, have been reported to have impaired salivary gland function and protein composition. 26 Thus, the aim of the present study was to identify salivary proteins from breast and ovarian cancer patients that could be indicative of metastatic breast and ovarian cancers.…”

mentioning

confidence: 99%

In search of the altering salivary proteome in metastatic breast and ovarian cancers

2019

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Breast and ovarian cancers, the most common cancers in women in India, are expected to rise in the next decade. Metastatic organotropism is a nonrandom, predetermined process which represents a more lethal and advanced form of cancer with increased mortality rate. In an attempt to study organotropism, salivary proteins were analyzed by mass spectrometry indicative of pathophysiology of breast and ovarian cancers and were compared to healthy and ovarian chemotherapy subjects. Collectively, 646 proteins were identified, of which 409 proteins were confidently identified across all four groups. Network analysis of upregulated proteins such as coronin‐1A, hepatoma‐derived growth factor, vasodilator‐stimulated phosphoprotein (VASP), and cofilin in breast cancer and proteins like coronin‐1A, destrin, and HSP90α in ovarian cancer were functionally linked and were known to regulate cell proliferation and migration. Additionally, proteins namely VASP, coronin‐1A, stathmin, and suprabasin were confidently identified in ovarian chemotherapy subjects, possibly in response to combined paclitaxel and carboplatin drug therapy to ovarian cancer. Selected representative differentially expressed proteins (eg, gelsolin, VASP) were validated by western blot analysis. Results of this study provide a foundation for future research to better understand the organotropic behavior of breast and ovarian cancers, as well as neoadjuvant drug response in ovarian cancer.

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“…Liquid biopsy can derive numerous genetic and proteomic information of primary and metastatic cancer, estimate the cellular and molecular characteristics of cancer-associated cells, and monitor the response to different anticancer therapies [129]. It is worth mentioning that liquid biopsies can be performed by using blood [130,131], saliva [132][133][134], urine [135][136][137], stool [138,139], semen, sweat, tear, nasal mucus, milk, and cerebrospinal fluid [140][141][142].…”

Section: Cancer Liquid Biopsiesmentioning

confidence: 99%

Roles of Extracellular Vesicles (EVs) Carrying HSPs in Cancer Biomarkers, Immune Surveillance, and Immune Evasion

Taha¹,

Ono²,

Eguchi³

2019

Preprint

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Extracellular vesicles (EV) released by tumor cells are a major aspect of the resistance-associated secretory phenotype (RASP), by which immune evasion can be established. Heat shock proteins (HSPs) are an evolutionarily conserved family of molecular chaperones, which stabilize proteins, minimize protein misfolding and aggregation within the cell, besides facilitating protein translocation, refolding and degradation. (i) Releases of extracellular HSPs (ex-HSP) and EV-associated HSPs (EV-HSP) are essential in RASP, by which molecular cotransfer of HSPs with oncogenic factors into recipient cells can promote cancer progression and resistance against stress such as hypoxia, radiation, chemicals, and immune system. (ii) RASP of tumor cells can eject anticancer drugs, molecularly targeted therapeutics, and immune checkpoint inhibitors with EVs. (iii) Cytotoxic lipids can be also released from tumor cells as RASP. Nevertheless, ex-HSP and EV-HSP can play immunostimulatory and immunosuppressive roles by binding to receptors such as LRP1/CD91/A2MR, scavenger receptors, and toll-like receptors expressed on recipient cells. Liquid biopsy of HSPs in body fluids may be useful in diagnosis, prognosis, and treatment in cancer. Regarding HSP90-targeted therapeutics, we summarize the pros, cons, and problem solutions in this review. Although production of HSPs are canonically induced by heat shock factor 1 (HSF1) and hypoxia-inducible factor 1 (HIF-1), recent studies discovered that production of HSPs is also regulated by matrix metalloproteinase 3 (MMP3) and heterochromatin protein 1 (HP1) and production of cochaperone CDC37 is reciprocally regulated by myeloid zinc finger 1 (MZF1) and SCAN-D1.

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Cancer Salivary Biomarkers for Tumours Distant to the Oral Cavity

Cited by 29 publications

References 87 publications

Roles of Extracellular HSPs as Biomarkers in Immune Surveillance and Immune Evasion

Roles of Extracellular HSPs as Biomarkers in Immune Surveillance and Immune Evasion

In search of the altering salivary proteome in metastatic breast and ovarian cancers

Roles of Extracellular Vesicles (EVs) Carrying HSPs in Cancer Biomarkers, Immune Surveillance, and Immune Evasion

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