Angiogenesis as a hallmark of solid tumors - clinical perspectives

Majidpoor, Jamal; Mortezaee, Keywan

doi:10.1007/s13402-021-00602-3

Cited by 175 publications

(83 citation statements)

References 165 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Consequently, the microchannels allow for increased passive oxygen and nutrient diffusion. Tumor cells may also follow along the blood vessels, whereby the blood vessel structures act as guides, allowing tumor cells to spread both internally into and externally around existing blood vessels ( Ge and Luo, 2018 ; Zavyalova et al, 2019 ; Fathi Maroufi et al, 2020 ; Mei et al, 2020 ; Wechman et al, 2020 ; Zhang et al, 2020 ; Majidpoor and Mortezaee, 2021 ; Ribatti and Pezzella, 2021 ; Treps et al, 2021 ; Wei et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Transmembrane Protein TMEM230, a Target of Glioblastoma Therapy

Cocola

Magnaghi

Abeni

et al. 2021

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Glioblastomas (GBM) are the most aggressive tumors originating in the brain. Histopathologic features include circuitous, disorganized, and highly permeable blood vessels with intermittent blood flow. These features contribute to the inability to direct therapeutic agents to tumor cells. Known targets for anti-angiogenic therapies provide minimal or no effect in overall survival of 12–15 months following diagnosis. Identification of novel targets therefore remains an important goal for effective treatment of highly vascularized tumors such as GBM. We previously demonstrated in zebrafish that a balanced level of expression of the transmembrane protein TMEM230/C20ORF30 was required to maintain normal blood vessel structural integrity and promote proper vessel network formation. To investigate whether TMEM230 has a role in the pathogenesis of GBM, we analyzed its prognostic value in patient tumor gene expression datasets and performed cell functional analysis. TMEM230 was found necessary for growth of U87-MG cells, a model of human GBM. Downregulation of TMEM230 resulted in loss of U87 migration, substratum adhesion, and re-passaging capacity. Conditioned media from U87 expressing endogenous TMEM230 induced sprouting and tubule-like structure formation of HUVECs. Moreover, TMEM230 promoted vascular mimicry-like behavior of U87 cells. Gene expression analysis of 702 patients identified that TMEM230 expression levels distinguished high from low grade gliomas. Transcriptomic analysis of patients with gliomas revealed molecular pathways consistent with properties observed in U87 cell assays. Within low grade gliomas, elevated TMEM230 expression levels correlated with reduced overall survival independent from tumor subtype. Highest level of TMEM230 correlated with glioblastoma and ATP-dependent microtubule kinesin motor activity, providing a direction for future therapeutic intervention. Our studies support that TMEM230 has both glial tumor and endothelial cell intracellular and extracellular functions. Elevated levels of TMEM230 promote glial tumor cell migration, extracellular scaffold remodeling, and hypervascularization and abnormal formation of blood vessels. Downregulation of TMEM230 expression may inhibit both low grade glioma and glioblastoma tumor progression and promote normalization of abnormally formed blood vessels. TMEM230 therefore is both a promising anticancer and antiangiogenic therapeutic target for inhibiting GBM tumor cells and tumor-driven angiogenesis.

show abstract

Section: Discussionmentioning

confidence: 99%

Transmembrane Protein TMEM230, a Target of Glioblastoma Therapy

Cocola

Magnaghi

Abeni

et al. 2021

Front. Cell. Neurosci.

View full text Add to dashboard Cite

show abstract

“…There is evidence that angiogenesis in adult lungs is generally limited, except in pathological conditions such as tumor growth, wound healing, or fibrosis. With respect to tumor growth, there is a non-angiogenic process described as vessel co-option, which is an alternative mechanism of generating the blood supply that differs fundamentally from the well-known sprouting angiogenesis and occurs in a significant fraction in highly vascularized organs like lung, brain, and colon [51][52][53][54][55]. Here tumor cells grow into preexisting mature blood vessels independently of stimulating new blood vessel formation.…”

Section: Discussionmentioning

confidence: 99%

Coalescent angiogenesis—evidence for a novel concept of vascular network maturation

et al. 2021

View full text Add to dashboard Cite

Angiogenesis describes the formation of new blood vessels from pre-existing vascular structures. While the most studied mode of angiogenesis is vascular sprouting, specific conditions or organs favor intussusception, i.e., the division or splitting of an existing vessel, as preferential mode of new vessel formation. In the present study, sustained (33-h) intravital microscopy of the vasculature in the chick chorioallantoic membrane (CAM) led to the hypothesis of a novel non-sprouting mode for vessel generation, which we termed “coalescent angiogenesis.” In this process, preferential flow pathways evolve from isotropic capillary meshes enclosing tissue islands. These preferential flow pathways progressively enlarge by coalescence of capillaries and elimination of internal tissue pillars, in a process that is the reverse of intussusception. Concomitantly, less perfused segments regress. In this way, an initially mesh-like capillary network is remodeled into a tree structure, while conserving vascular wall components and maintaining blood flow. Coalescent angiogenesis, thus, describes the remodeling of an initial, hemodynamically inefficient mesh structure, into a hierarchical tree structure that provides efficient convective transport, allowing for the rapid expansion of the vasculature with maintained blood supply and function during development.

show abstract

“…Vascular endothelial growth factor (VEGF) is a pro-angiogenic factor that is overexpressed in tumors, and its persistent hyper-release in TME promotes vascular immaturity and abnormal angiogenesis, delineated by leaky (or permeable) vessels ( 110 ). Cancer-associated fibroblasts (CAFs), M2 cells, cancer cells, and ECs are the four key sources of VEGF in TME ( 111 ). VEGF overexpression acts as a promoter of an immature vascular net ( 112 ), and that development of such immature vessels has a profound impact on tumor progression, mediated through promoting immunosuppression and therapy resistance ( 111 ).…”

Section: Factors Related To the Immaturity In Tumor Immune Ecosystemmentioning

confidence: 99%

“…Cancer-associated fibroblasts (CAFs), M2 cells, cancer cells, and ECs are the four key sources of VEGF in TME ( 111 ). VEGF overexpression acts as a promoter of an immature vascular net ( 112 ), and that development of such immature vessels has a profound impact on tumor progression, mediated through promoting immunosuppression and therapy resistance ( 111 ). VEGF has an inhibitory effect on maturation of MDSCs into APCs ( 113 ).…”

Section: Factors Related To the Immaturity In Tumor Immune Ecosystemmentioning

confidence: 99%

(Im)maturity in Tumor Ecosystem

Mortezaee

Majidpoor

2022

Front. Oncol.

Self Cite

View full text Add to dashboard Cite

Tumors have special features that make them distinct from their normal counterparts. Immature cells in a tumor mass and their critical contributions to the tumorigenesis will open new windows toward cancer therapy. Incomplete cellular development brings versatile and unique functionality in the cellular tumor ecosystem, such as what is seen for highly potential embryonic cells. There is evidence that maturation of certain types of cells in this ecosystem can recover the sensitivity of the tumor. Therefore, understanding more about the mechanisms that contributed to this immaturity will render new therapeutic approaches in cancer therapy. Targeting such mechanisms can be exploited as a supplementary to the current immunotherapeutic treatment schedules, such as immune checkpoint inhibitor (ICI) therapy. The key focus of this review is to discuss the impact of (im)maturity in cellular tumor ecosystems on cancer progression, focusing mainly on immaturity in the immune cell compartment of the tumor, as well as on the stemness of tumor cells.

show abstract

Angiogenesis as a hallmark of solid tumors - clinical perspectives

Cited by 175 publications

References 165 publications

Transmembrane Protein TMEM230, a Target of Glioblastoma Therapy

Transmembrane Protein TMEM230, a Target of Glioblastoma Therapy

Coalescent angiogenesis—evidence for a novel concept of vascular network maturation

(Im)maturity in Tumor Ecosystem

Contact Info

Product

Resources

About