Invasion and metastasis control: implications for increased therapeutic index of antitumor drugs

Mareel, Marc; Bracke, Marc; Bruyneel, Erik; Larebeke, N. Van; Mets, M. De

doi:10.1016/0305-7372(90)90066-o

Cited by 4 publications

(1 citation statement)

References 10 publications

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“…Interestingly, increasing evidence suggests a role for lipid rafts in metastasis [101][102][103][104][105][106]. In this regard, ALPs have been shown to inhibit metastasis and cell invasion [107][108][109][110][111][112][113], and a patent showed that edelfosine treatment could be useful and feasible for long-term palliative treatment of brain tumors, leading to tumor stabilization in a high proportion of patients that had previously received several treatments [114]. During this phase II study [114], the adverse drug reactions caused by edelfosine therapy were rather mild and had a short duration.…”

Section: New Patents Involving Alps and Their Pu-tative Action On Lipmentioning

confidence: 99%

Lipid Rafts and Fas/CD95 Signaling in Cancer Chemotherapy

Gajate

Mollinedo

2011

PRA

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Cholesterol- and sphingolipid-rich membrane domains, termed lipid rafts, have been recently involved in the triggering of death receptor-mediated apoptosis. The alkyl-lysophospholipid analogue edelfosine was the first antitumor drug reported to induce apoptosis in cancer cells through co-clustering of lipid rafts and Fas/CD95 death receptor. Recruitment and aggregation of Fas/CD95 in lipid raft clusters was independent of its cognate ligand FasL/CD95L, and could be pharmacologically modulated. The adaptor molecule Fas-associated death domain protein (FADD) and procaspase-8 were also recruited into lipid rafts following edelfosine treatment, forming the death-inducing signaling complex (DISC), and hence these membrane microdomains can act as scaffolds for Fas/CD95 death signaling. Edelfosine accumulated in lipid rafts of cancer cells, altering raft protein and lipid composition. Subsequently, an increasing number of antitumor drugs have been found to induce apoptosis through recruitment of Fas/CD95 into membrane rafts, and some of these compounds accumulated in raft membrane domains. Additional downstream apoptotic signaling molecules have also been reported to be recruited into rafts following treatment of cancer cells with antitumor agents, thus facilitating protein-protein interactions and conveying apoptotic signals. On these grounds, lipid rafts have become an appealing and promising target for therapeutic intervention in cancer chemotherapy. Co-clustering of lipid rafts and Fas/CD95 signaling provides a new insight in the regulation of death receptor-mediated apoptosis, opening a new avenue in cancer therapy. In this regard, an increasing number of patents are dealing with the above insights in order to improve cancer treatment.

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Section: New Patents Involving Alps and Their Pu-tative Action On Lipmentioning

confidence: 99%

Lipid Rafts and Fas/CD95 Signaling in Cancer Chemotherapy

Gajate

Mollinedo

2011

PRA

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Inhibition of collagenolytic activity relates to quantitative reduction of invasionin vitro in a c-Ha-ras transfected glial cell line

et al. 1994

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The function of proteases in brain tumor invasion is currently not well established. For tumors of epithelial and fibromatous origin collagenase production can enhance the invasive capacity of cells to penetrate basement membranes. We showed previously that a c-Ha-ras transformed glial cell line (CxT24neo3) invaded hamster brain tissue in vivo. These cells were also capable of invading reconstituted basement membrane and embryonic chick hearts in vitro. Since the histopathology of CxT24neo3 tumors mimics that of glioblastoma multiforme in humans, CxT24neo3 was used as the model in vitro for this type of brain tumor. Presently, we detected by zymogram analysis a gelatinase that was secreted by CxT24neo3 and that had an apparent molecular mass of 62 kD. To verify whether gelatinase affected invasion in vitro of these glial cells we determined the efficacy of a substrate specific collagenase inhibitor on invasion in vitro. GM6001 is a synthetic polypeptide that specifically occupies the substrate binding sites of metalloprotease. Since this drug did not show cytotoxicity, its specificity for metalloprotease is a valuable tool to evaluate the physiological function of these enzymes on invasion. We found that treatment of CxT24neo3 with GM6001 reduced the fraction of invading CxT24neo3 cells through reconstituted basement membrane. These data suggest that metalloproteases can stimulate brain tumor invasion.

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Analogs of alkyllysophospholipids: Chemistry, effects on the molecular level and their consequences for normal and malignant cells

Brachwitz

Vollgraf

1995

Pharmacology & Therapeutics

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Invasion and metastasis control: implications for increased therapeutic index of antitumor drugs

Cited by 4 publications

References 10 publications

Lipid Rafts and Fas/CD95 Signaling in Cancer Chemotherapy

Lipid Rafts and Fas/CD95 Signaling in Cancer Chemotherapy

Inhibition of collagenolytic activity relates to quantitative reduction of invasionin vitro in a c-Ha-ras transfected glial cell line

Analogs of alkyllysophospholipids: Chemistry, effects on the molecular level and their consequences for normal and malignant cells

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