Glycosaminoglycans in human lung cancer

Horai, Takeshi; Nakamura, Naotake; Tateishi, Ryuhei; Shoji, Hiromichi

doi:10.1002/1097-0142(19811101)48:9<2016::aid-cncr2820480918>3.0.co;2-a

Cited by 60 publications

(21 citation statements)

References 21 publications

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“…In addition, increasing evidence suggests the importance of HA in tumor progression (Knudson et al, 1989;Rooney et al, 1995;Knudson, 1996). Tumorspecific accumulation of HA was widely observed in human tumors, including colon cancer (Ropponen et al, 1998), lung cancer (Horai et al, 1981), breast cancer (Bertrand et al, 1992), and glioma (Delpech et al, 1993). In human glioma, inhibition of CD44 expression by an antisense oligonucleotide completely arrested the invasion (Merzak et al, 1994).…”

Section: Introductionmentioning

confidence: 98%

Hyaluronan Activates Cell Motility of v-Src-transformed Cells via Ras-Mitogen–activated Protein Kinase and Phosphoinositide 3-Kinase-Akt in a Tumor-specific Manner

Sohara

Ishiguro

Machida³

et al. 2001

MBoC

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We investigated the production of hyaluronan (HA) and its effect on cell motility in cells expressing the v-src mutants. Transformation of 3Y1 by v-src virtually activated HA secretion, whereas G2A v-src, a nonmyristoylated form of v-src defective in cell transformation, had no effect. In cells expressing the temperature-sensitive mutant of v-Src, HA secretion was temperature dependent. In addition, HA as small as 1 nM, on the other side, activated cell motility in a tumor-specific manner. HA treatment strongly activated the motility of v-Src-transformed 3Y1, whereas it showed no effect on 3Y1- and 3Y1-expressing G2A v-src. HA-dependent cell locomotion was strongly blocked by either expression of dominant-negative Ras or treatment with a Ras farnesyltransferase inhibitor. Similarly, both the MEK1 inhibitor and the kinase inhibitor clearly inhibited HA-dependent cell locomotion. In contrast, cells transformed with an active MEK1 did not respond to the HA. Finally, an anti-CD44-neutralizing antibody could block the activation of cell motility by HA as well as the HA-dependent phosphorylation of mitogen-activated protein kinase and Akt. Taken together, these results suggest that simultaneous activation of the Ras-mitogen-activated protein kinase pathway and the phosphoinositide 3-kinase pathway by the HA-CD44 interaction is required for the activation of HA-dependent cell locomotion in v-Src-transformed cells.

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Section: Introductionmentioning

confidence: 98%

Hyaluronan Activates Cell Motility of v-Src-transformed Cells via Ras-Mitogen–activated Protein Kinase and Phosphoinositide 3-Kinase-Akt in a Tumor-specific Manner

Sohara

Ishiguro

Machida³

et al. 2001

MBoC

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“…HAS1 exhibits higher enzymatic activity (Km) for both UDP-GlcNAc and UDP-GlcUA than HAS2 and HAS3. HAS3 synthesizes HA with molecular weights of 1x10 5 -1x10 6 Da, shorter than the HA synthesized by HAS1 and HAS2, which has molecular weights of 2x10 5 -2x10 6 Da. Moreover, HAS1 and HAS3 produce HA with broad size distributions, whereas HAS2 secrets extremely large HA (average molecular weight of >2x10 6 Da) (23,35,36).…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have suggested that increased production of hyaluronan (HA) is associated with metastatic behavior in certain types of malignant tumors, including breast cancer (2-4), lung cancer (5), colon cancer (6), and mesotheliomas (7). The increased levels of HA in the serum of some cancer patients are significantly elevated over those of normal individuals (6,8,9).…”

Section: Introductionmentioning

confidence: 99%

HAS3-related hyaluronan enhances biological activities necessary for metastasis of osteosarcoma cells

Tofuku

Yokouchi²,

Murayama³

et al. 2006

Int J Oncol

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Abstract. Several studies have suggested that increased production of hyaluronan (HA) is associated with metastatic behavior in various malignant tumors. To our knowledge, HA molecular weights required for metastasis are still unsolved in osteosarcoma. We examined the size of HA and hyaluronan synthase (HAS) isoforms related to biological functions required for metastasis in the LM8 stably highly metastatic osteosarcoma cell line. We found that HA of molecular weight which HAS3 produces enhanced biological functions related to metastasis such as cell proliferation, invasion, and degradation of extracellular matrix. Moreover, cell proliferation and invasion were inhibited by suppressing the activity of HAS3 expressed in LM8 cells, using hyaluronan synthase suppressor, 4-methylumbelliferone (MU). HA with the molecular weight related to HAS2 was the most adherent to CD44 in LM8 cells, suggesting that HAS2 may play an important role in pericellular coat formation. These results suggest that HAS3-related HA enhances crucial biological activities necessary for metastasis and that HAS2-related HA offers an advantageous environment for osteosarcoma cells.

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“…Merece destacarse que en los carcinomas broncoalveolares y adenocarcinomas su expresión es alta en las células en crecimiento y menor en las invasivas 9 . El ácido hialurónico (AH) es un glicosaminoglicano que se incrementa notablemente en el tejido pulmonar tumoral en relación al normal y ello es más acusado en el subtipo escamoso 10 . En líneas celulares tumorales el AH que rodea a las células tumorales escamosas puede proteger la migración y capacidad invasiva 11 ; asimismo, su unión al CD44 estándar (CD44s) potencia la secreción de ciertas metaloproteasas de matriz (MMP2) , lo que puede ser de interés en el proceso invasivo 12 .…”

Section: Introductionunclassified

Valor clínico-biológico de la concentración citosólica de ácido hialurónico en adenocarcinomas pulmonares CD44v6 positivos

Ruibal

Salmón²,

Argibay

et al. 2005

Oncología (Barc.)

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Resumen• Propósito: El objetivo de este estudio ha sido analizar la influencia de la concentración citosóli-ca de ácido hialurónico (AH) sobre las características clínico-biológicas de adenocarcinomas de pulmón CD44v6 positivos.• Material y métodos: El grupo estudio incluyó 34 muestras tumorales. Dosificamos las concentraciones citosólicas de AH, pS2, catepsina D, t-AP, NSE, cyfra 21.1, CA125 y fracción libre de la hormona gonadotrófica coriónica. También determinamos las concentraciones de EGFR, proteína oncogénica erbB2, CD44s y CD44v5 en las membranas celulares. Se tuvo presente, asimismo, el estadio clínico, grado histológico, ploidía, índice de DNA y fase de síntesis celular (FS).• • Conclusiones: Los resultados obtenidos parecen resaltar la importancia de la concentración citosólica de AH en los adenocarcinomas pulmonares CD44v6 positivos, de tal modo que altos valores en el índice AH/CD44v6 se asocian con una mayor proliferación e indiferenciación celular, lo cual unido a mayores concentraciones de proteína oncogénica erbB2, sugiere un subgrupo de tumores con un posible diferente comportamiento. Sin embargo, dada el reducido número de enfermos incluí-dos, creemos que son necesarios más estudios para poder confirmar nuestros hallazgos.

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Glycosaminoglycans in human lung cancer

Cited by 60 publications

References 21 publications

Hyaluronan Activates Cell Motility of v-Src-transformed Cells via Ras-Mitogen–activated Protein Kinase and Phosphoinositide 3-Kinase-Akt in a Tumor-specific Manner

Hyaluronan Activates Cell Motility of v-Src-transformed Cells via Ras-Mitogen–activated Protein Kinase and Phosphoinositide 3-Kinase-Akt in a Tumor-specific Manner

HAS3-related hyaluronan enhances biological activities necessary for metastasis of osteosarcoma cells

Valor clínico-biológico de la concentración citosólica de ácido hialurónico en adenocarcinomas pulmonares CD44v6 positivos

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