Impact of system L amino acid transporter 1 (LAT1) on proliferation of human ovarian cancer cells: A possible target for combination therapy with anti-proliferative aminopeptidase inhibitors

Fan, Xuetao; Ross, Douglas D.; Arakawa, Hiroshi; Ganapathy, Vadivel; Tamai, Ikumi; Nakanishi, Takeo

doi:10.1016/j.bcp.2010.05.021

Cited by 73 publications

(61 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SLC7A5 is overexpressed in many cancer types, including SCLC, and its expression levels are usually correlated to cancer progression and aggressiveness [14][15][16]. We demonstrated that in SCLC cells, similarly to other tumor types [17][18][19], suppression of SLC7A5 expression has an anti-proliferative effect. SCL7A5 suppression or miR-126 overexpression both delay SCLC cells in the G1 phase, suggesting that the effect of miR-126 on the cell cycle is at least in part mediated through SLC7A5.…”

Section: Discussionmentioning

confidence: 68%

miR-126 inhibits proliferation of small cell lung cancer cells by targeting SLC7A5

Margitai²,

et al. 2011

View full text Add to dashboard Cite

Edited by Tamas Dalmay Keywords:Small cell lung cancer miR-126 SLC7A5 G1 delay a b s t r a c t Despite intensive efforts to improve therapies, small cell lung cancer (SCLC) still has a dismal median survival of 18 months. Since miR-126 is under-expressed in the majority of SCLC tumors, we investigated the effect of miR-126 overexpression on the proliferation and cell cycle distribution of H69 cells. Our results demonstrate that miR-126 inhibits proliferation of H69 cells, by delaying the cells in the G1 phase. Short interfering RNA (siRNA) mediated suppression of SLC7A5, a predicted target of mir-126, has the same effect on H69 cells. We also show for the first time that SLC7A5 is a direct target of miR-126.

show abstract

Section: Discussionmentioning

confidence: 68%

miR-126 inhibits proliferation of small cell lung cancer cells by targeting SLC7A5

Margitai²,

et al. 2011

View full text Add to dashboard Cite

show abstract

“…The growth-stimulatory effect of androgens, including DHEAS, was evaluated by measuring cell growth after cells were plated at a density of 1.5 to 2.4 × 10 4 cells/cm 2 on a 96-well tissue culture plate. In general, once cells became attached to the plate, a test androgen or DMSO (at 0.1% of the final concentration) was added to the well, and cell growth was monitored for up to 9 days by means of sulforhodamine B (SRB, Sigma Aldrich) assay as previously described [17].…”

Section: Cell Culture and Growth Assaysmentioning

confidence: 99%

Enhanced expression of organic anion transporting polypeptides (OATPs) in androgen receptor-positive prostate cancer cells: Possible role of OATP1A2 in adaptive cell growth under androgen-depleted conditions

Arakawa

Nakanishi

Yanagihara

et al. 2012

Biochemical Pharmacology

Self Cite

View full text Add to dashboard Cite

The biological mechanisms underlying castration resistance of prostate cancer are not fully understood. In the present study, we examined the role of organic anion transporting polypeptides (OATPs) as importers of dehydroepiandrosterone sulfate (DHEAS) into cells to support growth under androgen-depleted conditions. Cell growth and mRNA expression of OATP genes were studied in human prostate cancer LNCaP and 22Rv1 cells under androgen-depleted conditions. The stimulatory effect of DHEAS on cell growth was investigated in LNCaP cells in which OATP1A2 had been silenced. Growth of both cell lines was stimulated by DHEAS and the effect was attenuated by STX64, an inhibitor of steroid sulfatase which can covert DHEAS to DHEA. OATP1A2 mRNA expression was increased most prominently among various genes tested in LNCaP cells grown in androgen-depleted medium. Similar results were obtained with 22Rv1 cells. Furthermore, the characteristics of

show abstract

“…3,4 Increased uptake of amino acids supports the high growth rate of cancer cells by providing the building blocks for protein synthesis. [4][5][6] Moreover, the higher expression of CD98 heavy chain and LAT-1 in metastatic vs. primary tumors suggests that over-expression of CD98/LAT-1 may facilitate progression and metastasis of human cancers.CD98 also regulates integrin signaling by association with integrin b-subunits, thereby controlling cell proliferation, survival, migration, epithelial adhesion and polarity. 3,7 The function of CD98 in regulating both amino acid transport and integrin signaling can contribute to the rapid proliferation and clonal expansion of lymphocytes and tumor cells.…”

mentioning

confidence: 99%

“…1,2 CD98 is overexpressed on the cell surface of almost all tumor cells, regardless of tissue origin and increased expression of a CD98-light chain, L-type amino acid transporter 1 (LAT-1) occurs in many types of human cancers, including breast, colon, oral, ovarian, esophageal, glioma and leukemia. 3,4 Increased uptake of amino acids supports the high growth rate of cancer cells by providing the building blocks for protein synthesis. [4][5][6] Moreover, the higher expression of CD98 heavy chain and LAT-1 in metastatic vs. primary tumors suggests that over-expression of CD98/LAT-1 may facilitate progression and metastasis of human cancers.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Antitumor activity of an anti‐CD98 antibody

et al. 2015

View full text Add to dashboard Cite

CD98 is expressed on several tissue types and specifically upregulated on fast-cycling cells undergoing clonal expansion. Various solid (e.g., nonsmall cell lung carcinoma) as well as hematological malignancies (e.g., acute myeloid leukemia) overexpress CD98. We have identified a CD98-specific mouse monoclonal antibody that exhibits potent preclinical antitumor activity against established lymphoma tumor xenografts. Additionally, the humanized antibody designated IGN523 demonstrated robust tumor growth inhibition in leukemic cell-line derived xenograft models and was as efficacious as standard of care carboplatin in patient-derived nonsmall lung cancer xenografts. In vitro studies revealed that IGN523 elicited strong ADCC activity, induced lysosomal membrane permeabilization and inhibited essential amino acid transport function, ultimately resulting in caspase-3 and -7-mediated apoptosis of tumor cells. IGN523 is currently being evaluated in a Phase I clinical trial for acute myeloid leukemia (NCT02040506). Furthermore, preclinical data support the therapeutic potential of IGN523 in solid tumors.CD98 is a heterodimeric protein that comprises a heavy and light chain. The CD98 heavy chain is a type II transmembrane glycoprotein that forms a heterodimer via covalent linkage to one of 6 amino acid transporters. 1,2 CD98 is overexpressed on the cell surface of almost all tumor cells, regardless of tissue origin and increased expression of a CD98-light chain, L-type amino acid transporter 1 (LAT-1) occurs in many types of human cancers, including breast, colon, oral, ovarian, esophageal, glioma and leukemia. 3,4 Increased uptake of amino acids supports the high growth rate of cancer cells by providing the building blocks for protein synthesis. [4][5][6] Moreover, the higher expression of CD98 heavy chain and LAT-1 in metastatic vs. primary tumors suggests that over-expression of CD98/LAT-1 may facilitate progression and metastasis of human cancers.CD98 also regulates integrin signaling by association with integrin b-subunits, thereby controlling cell proliferation, survival, migration, epithelial adhesion and polarity. 3,7 The function of CD98 in regulating both amino acid transport and integrin signaling can contribute to the rapid proliferation and clonal expansion of lymphocytes and tumor cells. 3 The expression pattern and pleiotropic function of CD98 heavy and light chains suggest these proteins are promising targets for treatment of a variety of human cancers. Although small molecule inhibitors of LAT-1 activity have demonstrated preclinical antitumor activity in a number of cancer cell types, including NSCLC, colon cancer, oral cancer and breast cancer, development of antibodies against CD98 heavy chain has received less focus. 5,[8][9][10] Murine monoclonal antibodies to CD98 inhibit lymphocyte proliferation and the growth of bladder cancer, lymphoma, glioma, prostate and colon cancer cells in preclinical models. [11][12][13] To identify therapeutic anti-CD98 antibodies with significant antitumor activity, we ...

show abstract

Impact of system L amino acid transporter 1 (LAT1) on proliferation of human ovarian cancer cells: A possible target for combination therapy with anti-proliferative aminopeptidase inhibitors

Cited by 73 publications

References 35 publications

miR-126 inhibits proliferation of small cell lung cancer cells by targeting SLC7A5

miR-126 inhibits proliferation of small cell lung cancer cells by targeting SLC7A5

Enhanced expression of organic anion transporting polypeptides (OATPs) in androgen receptor-positive prostate cancer cells: Possible role of OATP1A2 in adaptive cell growth under androgen-depleted conditions

Antitumor activity of an anti‐CD98 antibody

Contact Info

Product

Resources

About