Pericytes cross-talks within the tumor microenvironment

Picoli, Caroline C.; Gonçalves, Bryan Ôrtero Perez; Santos, Gabryella S P; Rocha, Beatriz G S; Costa, Alinne C.; Resende, Rodrigo R.; Birbrair, Alexander

doi:10.1016/j.bbcan.2021.188608

Cited by 28 publications

(23 citation statements)

References 156 publications

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“…The previous report suggests that low CP dose interacts with the variable types of tumor microenvironment (TME) cells, including tumor-infiltrating lymphoid cells, endothelial cells, pericytes, and recruited circulating endothelial cells ( Picoli et al, 2021 ). The anti-angiogenic mechanisms produced by CP have been identified by previous experimental studies, resulted in a declined microvessel density and then the enhancement of hypoxia ( Shahrzad et al, 2008 ; Laheurte et al, 2020 ).…”

Section: Resultsmentioning

confidence: 99%

Phthalimide Analogs Enhance Genotoxicity of Cyclophosphamide and Inhibit Its Associated Hypoxia

Gamal‐Eldeen

Agwa²,

Zahran

et al. 2022

Front. Chem.

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Cyclophosphamide (CP) is a mutagen that is used in cancer chemotherapy, due to its genotoxicity and as an immunosuppressive agent. Thalidomide (TH) is another cancer chemotherapeutic drug. In this study, the cytogenotoxicity and hypoxia modulatory activities of two phthalimide analogs of TH have been evaluated with/without CP. Both analogs have increased CP-stimulated chromosomal aberrations than those induced by TH, including gaps, breaks/fragments, deletions, multiple aberrations, and tetraploidy. The analogs have elevated the cytotoxic effect of CP by inhibiting the mitotic activity, in which analog 2 showed higher mitosis inhibition. CP has induced binucleated and polynucleated bone marrow cells (BMCs), while micronuclei (MN) are absent. TH and analogs have elevated the CP-stimulated binucleated BMCs, while only analogs have increased the CP-induced polynucleated BMCs and inhibited the mononucleated BMCs. MN-BMCs were shown together with mononucleated, binucleated, and polynucleated cells in the CP group. Both analogs have elevated mononucleated and polynucleated MN-BMCs, whereas in presence of CP, TH and analogs have enhanced mononucleated and binucleated MN-BMCs. The analogs significantly induce DNA fragmentation in a comet assay, where analog 1 is the strongest inducer. The treatment of mice with CP has resulted in a high hypoxia status as indicated by high pimonidazole adducts and high HIF-1α and HIF-2α concentrations in lymphocytes. Analogs/CP-treated mice showed low pimonidazole adducts. Both analogs have inhibited HIF-1α concentration but not HIF-2α. Taken together, the study findings suggest that both analogs have a higher potential to induce CP-genotoxicity than TH and that both analogs inhibit CP-hypoxia via the HIF-1α-dependent mechanism, in which analog 1 is a more potent anti-hypoxic agent than analog 2. Analog 1 is suggested as an adjacent CP-complementary agent to induce CP-genotoxicity and to inhibit CP-associated hypoxia.

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Section: Resultsmentioning

confidence: 99%

Phthalimide Analogs Enhance Genotoxicity of Cyclophosphamide and Inhibit Its Associated Hypoxia

Gamal‐Eldeen

Agwa²,

Zahran

et al. 2022

Front. Chem.

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“…Additionally, adipocytes directly interact with malignant cells affecting their behavior, including their proliferation and invasion capacities [139][140][141][142][143]. Adipocytes may also affect other components within the tumor microenvironment, such as newly formed blood vessels [144][145][146][147][148][149][150][151][152][153][154][155][156][157]. White and beige adipocytes, within the tumor microenvironment, also produce IL-6, and some of their effects on cancer cells have been attributed to IL-6 signaling [158,159].…”

Section: Interactions Within the Tumor Microenvironmentmentioning

confidence: 99%

Sympathetic nerve-adipocyte interactions in response to acute stress

et al. 2021

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“…and non-cellular components (cytokines, proteins, oxygen, etc.) (18)(19)(20)(21)(22). As the main component of TME, TAMs can interact with tumor cells by secreting cytokines, participating in CRC processes (23)(24)(25)(26).…”

Section: Introductionmentioning

confidence: 99%

Functional and Therapeutic Significance of Tumor-Associated Macrophages in Colorectal Cancer

Chen

Han

et al. 2022

Front. Oncol.

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The role of the tumor microenvironment (TME) in the progression of colorectal cancer (CRC) and its acquisition of resistance to treatment become the research hotspots. As an important component of TME, the tumor-associated macrophages (TAMs) regulate multiple critical oncogenic processes, namely, occurrence, proliferation, metastasis, and drug resistance in CRC. In this review, we have discussed the functional and therapeutic significance of TAMs in CRC. M1 macrophages act as the tumor suppressor while M2 macrophages promote CRC. The polarization of TAMs is mainly regulated by the pathways such as NFKB1 pathways, STAT3 pathways, WNT5A pathways, and PI3K pathways in CRC. Furthermore, the M2 polarization of TAMs is not only controllable but also reversible. Finally, we provide insights into the TAMs-targeted therapeutic strategies.

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Pericytes cross-talks within the tumor microenvironment

Cited by 28 publications

References 156 publications

Phthalimide Analogs Enhance Genotoxicity of Cyclophosphamide and Inhibit Its Associated Hypoxia

Phthalimide Analogs Enhance Genotoxicity of Cyclophosphamide and Inhibit Its Associated Hypoxia

Sympathetic nerve-adipocyte interactions in response to acute stress

Functional and Therapeutic Significance of Tumor-Associated Macrophages in Colorectal Cancer

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