Invadopodia are chemosensing protrusions that guide cancer cell extravasation to promote brain tropism in metastasis

Williams, Karla C.; Cepeda, Mario; Javed, Sumreen; Searle, Karlee; Parkins, Katie M.; Makela, Ashley V.; Hamilton, Amanda M.; Soukhtehzari, Sepideh; Kim, Young S.; Tuck, Alan B.; Ronald, John A.; Foster, Paula J.; Chambers, Ann F.; Leong, Hon S.

doi:10.1038/s41388-018-0667-4

Cited by 54 publications

(54 citation statements)

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“…Moreover, cancer cells can invade through the endothelium by projecting invadopodia [109]. Invadopodia are chemosensing protrusions that guide cancer cell extravasation to promote brain tropism in metastasis [110]. PAK1 (P21 (RAC1) Activated Kinase 1) is responsible for guiding cancer cell extravasation in BCBM [110].…”

Section: Extravasationmentioning

confidence: 99%

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microRNAs Orchestrate Pathophysiology of Breast Cancer Brain Metastasis: Advances in Therapy

et al. 2020

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Brain metastasis (BM) predominantly occurs in triple-negative (TN) and epidermal growth factor 2 (HER2)-positive breast cancer (BC) patients, and currently, there is an unmet need for the treatment of these patients. BM is a complex process that is regulated by the formation of a metastatic niche. A better understanding of the brain metastatic processes and the crosstalk between cancer cells and brain microenvironment is essential for designing a novel therapeutic approach. In this context, the aberrant expression of miRNA has been shown to be associated with BM. These non-coding RNAs/miRNAs regulate metastasis through modulating the formation of a metastatic niche and metabolic reprogramming via regulation of their target genes. However, the role of miRNA in breast cancer brain metastasis (BCBM) is poorly explored. Thus, identification and understanding of miRNAs in the pathobiology of BCBM may identify a novel candidate miRNA for the early diagnosis and prevention of this devastating process. In this review, we focus on understanding the role of candidate miRNAs in the regulation of BC brain metastatic processes as well as designing novel miRNA-based therapeutic strategies for BCBM.Keywords: Breast cancer brain metastasis, miRNA, Brain tumor microenvironment, Blood-brain barrier, CNS metastasis

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Section: Extravasationmentioning

confidence: 99%

“…Invadopodia are chemosensing protrusions that guide cancer cell extravasation to promote brain tropism in metastasis [110]. PAK1 (P21 (RAC1) Activated Kinase 1) is responsible for guiding cancer cell extravasation in BCBM [110]. PAK1 reduces the expression of miR-132 through the PAK1/ATF2/miR-132 axis.…”

Section: Extravasationmentioning

confidence: 99%

microRNAs Orchestrate Pathophysiology of Breast Cancer Brain Metastasis: Advances in Therapy

et al. 2020

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“…Metastasis is a complex and multistep process which involves tumor cell dissociation from the primary tumor, invasion of the surrounding extracellular matrix, intravasation through the endothelium into the bloodstream, and extravasation to secondary sites via attaching to endothelial cells and crossing the blood vessel walls. Finally, malignant cells survive and growth at these metastatic sites [94,95]. In order to invade and disseminate, tumor cells utilize dynamic actin-rich membrane protrusions named invadopodia which contain matrix proteases that degrade the extracellular matrix [94,96].…”

Section: Podxl In Metastasismentioning

confidence: 99%

“…Finally, malignant cells survive and growth at these metastatic sites [94,95]. In order to invade and disseminate, tumor cells utilize dynamic actin-rich membrane protrusions named invadopodia which contain matrix proteases that degrade the extracellular matrix [94,96]. In contrast to metastasis of solid cancers, which requires the acquisition of a metastatic phenotype, lymphoma dissemination is thought to be driven by physiological mechanisms governing normal lymphocyte trafficking [97,98].…”

Section: Podxl In Metastasismentioning

confidence: 99%

Emerging Role of Podocalyxin in the Progression of Mature B-Cell Non-Hodgkin Lymphoma

Tamayo-Orbegozo

Amo

Díez-García

et al. 2020

Cancers

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Mature B-cell non-Hodgkin lymphoma (B-NHL) constitutes a group of heterogeneous malignant lymphoproliferative diseases ranging from indolent to highly aggressive forms. Although the survival after chemo-immunotherapy treatment of mature B-NHL has increased over the last years, many patients relapse or remain refractory due to drug resistance, presenting an unfavorable prognosis. Hence, there is an urgent need to identify new prognostic markers and therapeutic targets. Podocalyxin (PODXL), a sialomucin overexpressed in a variety of tumor cell types and associated with their aggressiveness, has been implicated in multiple aspects of cancer progression, although its participation in hematological malignancies remains unexplored. New evidence points to a role for PODXL in mature B-NHL cell proliferation, survival, migration, drug resistance, and metabolic reprogramming, as well as enhanced levels of PODXL in mature B-NHL. Here, we review the current knowledge on the contribution of PODXL to tumorigenesis, highlighting and discussing its role in mature B-NHL progression.

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“…The CAM is commonly studied in a shell-less format (ex ovo), where xenograft human tumor fragments or a tumor cell suspension (Figure 2A) can be placed onto the CAM or injected into blood vessels of the CAM. The CAM has proven to be a useful model in studying tumor angiogenesis (90,91), tumor cell migration and invasion (92), intravasation into blood vessels (93), tumor cells in transit within the vasculature, extravasation out from blood vessels ( Figure 2B) (94)(95)(96)(97)(98), and the outgrowth of patient derived xenografts (99). In OS research, the CAM model has been used to study tumor growth of a variety of OS cell lines (100), angiogenesis (101), and metastasis to distant sites (102).…”

Section: Chick Chorioallantoic Membrane Modelmentioning

confidence: 99%

Understanding and Modeling Metastasis Biology to Improve Therapeutic Strategies for Combating Osteosarcoma Progression

2020

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Osteosarcoma is a malignant primary tumor of bone, arising from transformed progenitor cells with osteoblastic differentiation and osteoid production. While categorized as a rare tumor, most patients diagnosed with osteosarcoma are adolescents in their second decade of life and underscores the potential for life changing consequences in this vulnerable population. In the setting of localized disease, conventional treatment for osteosarcoma affords a cure rate approaching 70%; however, survival for patients suffering from metastatic disease remain disappointing with only 20% of individuals being alive past 5 years post-diagnosis. In patients with incurable disease, pulmonary metastases remain the leading cause for osteosarcoma-associated mortality; yet identifying new strategies for combating metastatic progression remains at a scientific and clinical impasse, with no significant advancements for the past four decades. While there is resonating clinical urgency for newer and more effective treatment options for managing osteosarcoma metastases, the discovery of druggable targets and development of innovative therapies for inhibiting metastatic progression will require a deeper and more detailed understanding of osteosarcoma metastasis biology. Toward the goal of illuminating the processes involved in cancer metastasis, a convergent science approach inclusive of diverse disciplines spanning the biology and physical science domains can offer novel and synergistic perspectives, inventive, and sophisticated model systems, and disruptive experimental approaches that can accelerate the discovery and characterization of key processes operative during metastatic progression. Through the lens of trans-disciplinary research, the field of comparative oncology is uniquely positioned to advance new discoveries in metastasis biology toward impactful clinical translation through the inclusion of pet dogs diagnosed with metastatic osteosarcoma. Given the spontaneous course of osteosarcoma development in the context of real-time tumor microenvironmental cues and immune mechanisms, pet dogs are distinctively valuable in translational modeling given their faithful recapitulation of metastatic disease

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Invadopodia are chemosensing protrusions that guide cancer cell extravasation to promote brain tropism in metastasis

Cited by 54 publications

References 50 publications

microRNAs Orchestrate Pathophysiology of Breast Cancer Brain Metastasis: Advances in Therapy

microRNAs Orchestrate Pathophysiology of Breast Cancer Brain Metastasis: Advances in Therapy

Emerging Role of Podocalyxin in the Progression of Mature B-Cell Non-Hodgkin Lymphoma

Understanding and Modeling Metastasis Biology to Improve Therapeutic Strategies for Combating Osteosarcoma Progression

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