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PubMed2001

Overexpression of insulin-like growth factor binding protein-6 inhibits rhabdomyosarcoma growth in vivo.

Rhabdomyosarcoma is the most common soft-tissue sarcoma of childhood. Rhabdomyosarcoma cell lines overexpress insulin-like growth factor-II (IGF-II), an autocrine growth factor that is inhibited by insulin-like growth factor binding protein-6 (IGFBP-6). IGFBP-6 is associated with myoblast quiescence, and expression in rhabdomyosarcoma cells is low. The effect of IGFBP-6 on 2 rhabdomyosarcoma cell lines, RD and Rh30, was studied. IGFBP-6 inhibited anchorage-dependent growth of RD and Rh30 cells in a dose-dependent manner (p < 0.0001). IGFBP-6 also inhibited anchorage-independent growth of RD cells in soft agar in a dose-dependent manner (p < 0.01). Anchorage-independent growth of RD cells on polyhydroxyethylmethacrylate-coated plates was decreased to a minimum of 48% of control after treatment with IGFBP-6 (p < 0.001). In this system, IGFBP-6 increased apoptosis 4-fold (p < 0.001). IGF-II partially reversed the IGFBP-6-induced decrease in growth and increase in apoptosis. Rh30 cells were stably transfected with an IGFBP-6 cDNA and subcutaneous xenografts established in BALB/c nude mice. After 18 days, sizes of 2 independent clones of IGFBP-6-overexpressing Rh30 cells were reduced to 12% and 26% of vector control-transfected tumors (p = 0.0006 and 0.002, respectively). IGFBP-6 therefore inhibits proliferation and promotes apoptosis of rhabdomyosarcoma in vitro and dramatically inhibits xenograft growth in vivo, at least in part by inhibiting IGF-II. Low expression of IGFBP-6 may therefore contribute to rhabdomyosarcoma growth and metastasis.

Animals↗
PubMed1989

Rhabdomyosarcoma in children: a histological and immunohistochemical study of 59 cases.

Recent studies have suggested that rhabdomyosarcoma can be divided into favourable and unfavourable histology groups. Those subtypes comprising the unfavourable histology group are alveolar, monomorphous round cell and anaplastic rhabdomyosarcoma, with a favourable histology group of embryonal rhabdomyosarcomas. An immunohistological study was undertaken on 59 childhood rhabdomyosarcomas, using antisera to keratin, S100 protein, vimentin, desmin, myoglobin, and troponin T. Our results suggest that desmin is the single most useful antibody in the diagnosis of rhabdomyosarcoma and was expressed in all our cases. The expression of troponin T in the majority of embryonal rhabdomyosarcomas but not in the other histological types has prognostic implications.

Child↗
PubMed2004

Sclerosing rhabdomyosarcoma in childhood: case report and review of the literature.

Rhabdomyosarcoma is the most common soft tissue malignancy in children but is rare in adults. The latest World Health Organization classification of soft tissue tumors recognizes embryonal, alveolar, and pleomorphic rhabdomyosarcomas. More recently, a sclerosing variant of rhabdomyosarcoma has been recognized and reported in seven adult patients. We describe a pediatric case of sclerosing rhabdomyosarcoma presenting as a sacral mass in a 3-year-old girl. Morphologically, the tumor showed a prominent sclerosing hyaline matrix and demonstrated pseudovascular and microalveolar architectural foci. Focal positivity was seen with desmin, smooth muscle actin, and myogenin. MyoD1 showed uniform diffuse nuclear staining. Fusion transcripts were not demonstrated by reverse transcriptase-polymerase chain reaction analysis. The histology, immunohistochemistry, and molecular genetics matched those reported in the seven adult cases of sclerosing rhabdomyosarcoma. This is the first case report, to our knowledge, of this rare tumor arising in the pediatric age group, and we compare the features with those reported in adult sclerosing rhabdomyosarcoma.

Child, Preschool↗
PubMed2001

Ophthalmic involvement as a presenting feature of nonorbital childhood parameningeal embryonal rhabdomyosarcoma.

OBJECTIVE: To describe presenting ophthalmic signs and symptoms in children with parameningeal rhabdomyosarcoma. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Twenty-three children with parameningeal rhabdomyosarcoma treated from 1978 through 1998. MAIN OUTCOME MEASURES: Each patient's presenting symptoms and history, the ophthalmic signs at presentation, the location of the tumor on computed tomographic scanning, the pathologic diagnosis after tumor biopsy, and the child's outcome after chemotherapy and radiotherapy. RESULTS: Eight of 23 patients with parameningeal rhabdomyosarcoma had ophthalmologic signs at presentation. All patients had sixth nerve palsies, and four had additional third nerve palsies. Fifth and seventh nerve involvement was seen in three children each, and two manifested additional fourth nerve palsies. In two patients, invasion of the optic canals and posterior orbit resulted in unilateral blindness in one and marked unilateral visual loss in the other. In no patient was the symptomatic history longer than 12 weeks. Seven of eight patients were treated with a combination of surgery, chemotherapy, and radiotherapy. The mean survival time for five patients who died from parameningeal rhabdomyosarcoma associated with ophthalmic signs was 27.2 months. Three patients are currently alive, with a mean survival time of 33.7 months after diagnosis. The survival time of 12 patients with parameningeal rhabdomyosarcoma and without ophthalmologic signs at presentation was better, in that nine are alive, with a mean survival time of 54 months. CONCLUSIONS: Advanced parameningeal rhabdomyosarcoma with skull base invasion may present with ophthalmic signs. These patients sought treatment late and had advanced tumors because their initial signs and symptoms were often attributed to more common ailments. Usually, the onset of the cranial nerve palsy initiated referral to the tertiary care center. The sixth nerve was the most vulnerable. Further invasion of the skull base or cavernous sinus may cause additional third, fourth, and fifth nerve palsies. The optic nerve was involved when the optic canals and orbit were encroached on by the tumor. The prognosis for survival was poor when these tumors were accompanied by ophthalmic signs.

Child↗
PubMed2001

Clinical spectrum of primary ophthalmic rhabdomyosarcoma.

PURPOSE: To review the clinical presentation, histopathologic analysis, management, and ocular and systemic outcome of rhabdomyosarcoma affecting the ocular region. DESIGN: Retrospective, noncomparative, consecutive, interventional case series. PARTICIPANTS: Thirty-three consecutive patients with primary ophthalmic involvement of rhabdomyosarcoma from a single tertiary care center specializing in ocular oncology. MAIN OUTCOME MEASURES: Final visual acuity, treatment complications, local recurrence, and distant metastasis. RESULTS: The mean age at presentation was 10 years (median, 7 years; range, 1 month-68 years). At presentation, 8 patients (24%) were older than age 10 years and 4 patients (12%) were older than 20 years. The rhabdomyosarcoma was primarily located in the orbit in 25 cases (76%), conjunctiva in 4 cases (12%), eyelid in 1 case (3%), and uveal tract in 3 cases (9%). Symptoms or signs related to the tumor were present for a mean of 5 weeks and included proptosis in 10 patients (30%), eyelid swelling in 7 patients (21%), and blepharoptosis in 6 patients (18%). The initial diagnosis before referral to us included rhabdomyosarcoma in 8 cases (24%), conjunctivitis in 5 cases (15%), orbital or preseptal cellulitis in 5 cases (15%), idiopathic orbital inflammatory pseudotumor in 4 cases (12%), and others. Using the Intergroup Rhabdomyosarcoma Study Group staging and treatment protocols, the tumor was classified as group I in 4 cases (12%), group II in 12 cases (36%), group III in 16 cases (48%), and group IV in 1 case (3%). Treatment included surgical debulking and various regimens of chemotherapy and radiotherapy for the periocular tumors and enucleation for the three intraocular tumors. Local tumor recurrence was detected in 6 patients (18%). Orbital exenteration was necessary for tumor recurrence in 2 cases (6%). Long-term visual outcome of the 28 patients who maintained their globe was 20/20 to 20/40 in 11 patients (39%), 20/50 to 20/100 in 5 patients (18%), and 20/200 to no light perception in 12 patients (43%). Regional lymph node metastasis was detected in 2 patients (6%), one at initial visit and one after therapy. Distant metastasis occurred in 2 patients (6%), one detected at initial visit and one after therapy. With mean follow-up of 8.3 years, tumor-related death occurred in 1 patient (3%). CONCLUSIONS: Rhabdomyosarcoma can present in the orbit, eyelid, conjunctiva, and uveal tract. After treatment, local tumor recurrence occurs in 18%, metastasis in 6%, and death in 3%.

Adolescent↗
PubMed2001

Identification of new genes related to the myogenic differentiation arrest of human rhabdomyosarcoma cells.

Rhabdomyosarcoma is a soft tissue tumor committed to the myogenic lineage but arrested prior to terminal differentiation. To identify new genes implicated in the block in myogenic differentiation of rhabdomyosarcoma cells and those responsible for their proceeding along the myogenic pathway we used cDNA microarrays to compare gene expression profiles of two clones of the human embryonal rhabdomyosarcoma cell line RD with different myogenic potentials: RD/12, which is unable to differentiate, and RD/18, which shows elements able to terminally differentiate, as defined by the expression of myosin heavy chain (up to 50% of the population) and the formation of multinucleated myotube-like structures. We identified 80 genes differentially expressed by the two clones. Differentiating RD/18 cells overexpressed the myogenic transcription factor myogenin along with known myogenic markers; myogenin transfection into undifferentiated RD/12 cells was able to revert the phenotype giving rise to 94% of clones displaying a differentiated morphology. RD/18 cells also expressed several genes not known to be expressed in rhabdomyosarcoma or muscle cells, such as pigment-epithelium derived factor and endothelin-3. Poorly differentiated RD/12 cells, along with genes related to mesenchymal lineage or early myogenic commitment, also expressed genes not previously known to be related to the differentiation block of human rhabdomyosarcoma, such as monocyte chemotactic protein-1, connective tissue growth factor and insulin-like growth factor binding protein-5. Differential expression of these genes in a time course of differentiation suggested their potential roles as either new myogenic markers or repressors of differentiation. These results identify a cluster of new genes related to the aberrant myogenic differentiation program of human rhabdomyosarcoma cells.

Cell Differentiation↗
PubMed1976

Pleomorphic rhabdomyosarcoma of the larynx. A case report and review of the literature.

A case of pleomorphic rhabdomyosarcoma of the larynx occurring in a 33-year-old male is reported. The clinical and histopathological aspects of this undoubtedly rare neoplasm are described. After a quick review of the most important classifications of rhabdomyosarcoma so far made, the authors suggest a division into two basic groups, i.e. pleomorphic and fetal rhabdomyosarcoma, while the botryoid sarcoma and the alveolar rhabdomyosarcoma should be considered only as two subgroups of fetal rhabdomyosarcoma. From a comprehensive review of world literature on the subject, the well-documented cases up to now described are only seven, including the authors. The present case is the third one after the instances of pleomorphic rhabdomyosarcoma reported by Filipo and Crifo (1964 and by Rodriquez and Ziskind (1970).

Adult↗
PubMedDate not supplied

Rhabdomyosarcoma of the uterus: report of two cases, including one of the spindle cell variant.

Most uterine sarcomas fall into the category of leiomyosarcoma, endometrial stromal sarcoma, or undifferentiated sarcoma. Pure rhabdomyosarcomas are extremely rare, although a rhabdomyosarcomatous element may be present as a component of an adenosarcoma or carcinosarcoma (malignant mixed müllerian tumor). This report describes two uterine rhabdomyosarcomas in 28- and 67-year-old women. These were of spindle cell and pleomorphic types, respectively. At presentation the pleomorphic rhabdomyosaroma was stage IV, exhibiting massive pelvic and abdominal dissemination that mimicked an ovarian neoplasm. The spindle cell rhabdomyosarcoma was stage I, being confined to the uterus. Grossly, both uterine tumors had a polypoid appearance. Immunohistochemically, tumor cells were positive with the skeletal muscle markers sarcomeric actin, myoglobin, and myoD1. The patient with stage IV disease died within a short time of diagnosis and the other patient is alive and well at 2 years' follow-up. This report adds to the published literature on uterine rhabdomyosarcomas. This is the first reported uterine case of the spindle cell variant of embryonal rhabdomyosarcoma. Based on these cases and the published literature, rhabdomyosarcoma, especially the pleomorphic variant, appears to be a very aggressive neoplasm with an extremely poor prognosis. Immunohistochemical demonstration of skeletal muscle differentiation is necessary for a definitive diagnosis.

Actins↗
PubMed1985

Skeletal muscle actin as tumor marker in the diagnosis of rhabdomyosarcoma in childhood.

Immunoaffinity-purified and tissue-specific antibodies against carp skeletal muscle actin have been assessed for their usefulness in diagnosing rhabdomyosarcoma. Routinely processed formaldehyde-fixed tissue and the avidin--biotinyl--peroxidase complex technique were used. Thirty-six tumors of patients varying in age from less than 1 year to 17 years were diagnosed as rhabdomyosarcoma on the basis of routine histological stains or electron microscopy, and on clinical grounds. Among them were 20 poorly differentiated tumors. All moderately and well-differentiated rhabdomyosarcomas and the majority of the poorly differentiated tumors (13 of 20) showed positive immunostaining for actin. Positive staining was observed in all three types of rhabdomyosarcoma, i.e., embryonal, alveolar, and pleomorphic. Besides rhabdomyosarcomas, the only other positive neoplasms were those that contained rhabdomyoblastic differentiation such as malignant "triton" tumors and malignant mixed müllerian tumors. Our results indicate that antibodies against skeletal muscle actin are a powerful tool for diagnosing rhabdomyosarcoma and that they can be used to distinguish the poorly differentiated forms from other types of small round cell tumors in childhood such as neuroblastoma, Ewing's sarcoma, and malignant lymphoma. The results are discussed in the light of the embryogenesis of cross-striated skeletal muscle.

Actins↗
PubMedDate not supplied

HER/erbB receptors as therapeutic targets of immunotoxins in human rhabdomyosarcoma cells.

Human rhabdomyosarcoma cells express HER/erbB growth factors receptors. Receptors belonging to this family are overexpressed and play a role in many types of epithelial and neural cancer and have been selected as targets for cancer therapy. In this paper EGF-R, HER-2 and HER-3 receptors were tested as therapeutic targets of immunotoxins in human rhabdomyosarcoma. Rhabdomyosarcoma cells were treated with indirect immunotoxins consisting in primary specific murine monoclonal antibodies recognizing EGF-R, HER-2 and HER-3 followed by secondary F(ab')2 antimouse immunoglobulin linked to saporin-S6, a type 1 ribosome-inactivating protein (RIP) from the seeds of Saponaria officinalis. The indirect immunotoxin targeting EGF-R caused a significant inhibition in cell growth and protein synthesis and a strong increase in apoptosis in rhabdomyosarcoma cells, whereas indirect immunotoxins against HER-2 and HER-3 were ineffective. The toxic activity of anti-EGF-R immunotoxin was also observed on rhabdomyosarcoma cells expressing low level of EGF-R. EGF-R could be a novel therapeutic target of immunotoxins in human rhabdomyosarcoma.

Antibodies, Monoclonal↗
PubMed1983

Immunohistochemistry of myoglobin in rhabdomyosarcomas.

Immunoperoxidase staining for myoglobin was performed on formalin-fixed, paraffin-embedded tissues of normal human skeletal muscle and rhabdomyosarcomas in order to assess its potential diagnostic value. Myoglobin-positive cells were observed in normal adult and fetal muscles, and in 13 of 26 rhabdomyosarcomas. In normal skeletal muscle, the intensity of staining for myoglobin varied in individual cells. Of the 13 myoglobin-positive rhabdomyosarcomas tested, 6 showed cross striations in tumor cells, whereas the others did not. Myoglobin-positive tumor cells were not demonstrated in two rhabdomyosarcomas in which cross striations were observed. In other types of tumors examined that sometimes resembled rhabdomyosarcomas, no myoglobin was detected. Thus tests for myoglobin by the immunoperoxidase method seem helpful in identifying rhabdomyosarcomas and confirming their histological diagnosis.

Adolescent↗
PubMedDate not supplied

Rhabdomyosarcoma of the urachus. A case report.

BACKGROUND: Rhabdomyosarcoma of the urachus is extremely rare, and only two cases have been reported. Cytologic, histologic, immunochemical and electron microscopic findings in embryonal rhabdomyosarcoma of the urachus are presented. CASE: Embryonal rhabdomyosarcoma of the urachus developed in a 2-year-old boy. Imprint smears prepared prior to a histologic examination for a rapid report contained many malignant cells isolated or in clusters in a myxoid background. They were uniformly small, with round to oval nuclei and scant cytoplasm, and immunohistochemically positive for desmin and alpha-sarcomeric muscle actin but negative for myoglobin. This tumor was diagnosed cytologically as embryonal rhabdomyosarcoma because of its skeletal muscle origin and because of its similarity to one of the so-called small round cell tumors of childhood. Histologic examination confirmed the cytologic diagnosis. CONCLUSION: Cytologic, histologic and electron microscopic findings were identical to those described previously for embryonal rhabdomyosarcoma at other sites. In immunochemical examinations, cytologic samples fixed in ethanol are more useful than histologic ones fixed in formalin. Then, in order to differentiate poorly differentiated rhabdomyosarcoma from other small round cell tumors in children, desmin and alpha-sarcomeric actin, rather than myoglobin, are recommended.

Actins↗
PubMed2001

Which patients with microscopic disease and rhabdomyosarcoma experience relapse after therapy? A report from the soft tissue sarcoma committee of the children's oncology group.

PURPOSE: To identify which patients with rhabdomyosarcoma and microscopic residual disease (group II) are likely to not respond to therapy. PATIENTS AND METHODS: Six hundred ninety-five patients with group II tumors received chemotherapy and 90% received radiation therapy on Intergroup Rhabdomyosarcoma Study (IRS)-I to IRS-IV (1972 to 1997). Tumors were subgrouped depending on the presence of microscopic residual disease only (subgroup IIa), resected positive regional lymph nodes, (subgroup IIb), or microscopic residual disease and resected positive regional lymph nodes (subgroup IIc). RESULTS: Overall, the 5-year failure-free survival rate (FFSR) was 73%, and patients with embryonal rhabdomyosarcoma treated on IRS-IV fared especially well (5-year FFSR, 93%; n = 90). Five-year FFSRs differed significantly by subgroup (IIa, 75% and n = 506; IIb, 74% and n = 101; IIc, 58% and n = 88; P = .0037) and treatment (IRS-I, 68%; IRS-II, 67%; IRS-III, 75%; IRS-IV, 87%; P < .001). Multivariate analysis revealed positive associations between primary site (favorable), histology (embryonal), subgroup IIa or IIb, treatment (IRS-III/IV), and better FFSRs. Patterns of treatment failure revealed local failure to be 8%, regional failure, 4%, and distant failure, 14%. The relapse pattern noted over the course of IRS-I to IRS-IV shows a decrease in the systemic relapse rates, particularly for patients with embryonal histology, suggesting that improvement in FFSRs is primarily a result of improved chemotherapy. CONCLUSION: Group II rhabdomyosarcoma has an excellent prognosis with contemporary therapy as used in IRS-III/IV, and those less likely to respond can be identified using prognostic factors: histology, subgroup, and primary site. Patients with embryonal rhabdomyosarcoma are generally cured, although patients with alveolar rhabdomyosarcoma or undifferentiated sarcoma, particularly subgroup IIc at unfavorable sites, continue to need better therapy.

Adolescent↗
PubMed2005

Relationship between MYCN copy number and expression in rhabdomyosarcomas and correlation with adverse prognosis in the alveolar subtype.

PURPOSE: Amplification of the transcription factor MYCN is an important molecular diagnostic tool in stratifying treatment for neuroblastoma. Increased copy number and overexpression of MYCN in the pediatric cancer rhabdomyosarcoma has been described in a number of small studies with conflicting conclusions about its association with clinicopathologic characteristics. We aimed to study the phenomenon in the largest series to date. PATIENTS AND METHODS: Using quantitative polymerase chain reaction, we measured MYCN copy number and expression levels in rhabdomyosarcoma samples from 113 and 92 individuals with a confirmed diagnosis of rhabdomyosarcoma, respectively. RESULTS: Increased copy number of MYCN was found to be a feature of both the embryonal and alveolar subtypes. The copy number and expression levels were significantly greater in the alveolar subtype, although the range of expression in both subtypes spanned several orders of magnitude. MYCN copy number showed a significant correlation with expression in the alveolar subtype; this relationship between copy number and expression could be modeled as a logarithmic function. It is notable that relatively high expression frequently occurred in embryonal rhabdomyosarcoma without high copy number and that low expression was found in some cases with high copy number. In patients with alveolar rhabdomyosarcoma, overexpression (greater than median) or gain of genomic copies of MYCN were significantly associated with adverse outcome. CONCLUSION: MYCN deregulation is a feature of rhabdomyosarcoma tumorigenesis, defines groups of patients with a poor prognosis, and is a potential target for novel therapies.

Child↗
PubMed1982

Rhabdomyosarcoma of the head and neck.

Rhabdomyosarcoma is an uncommon neoplasm that is seen in the head and neck area. Since the symptoms of rhabdomyosarcoma, such as aural discharge and nasal obstruction, mimic common disease states, the clinical diagnosis is often delayed. Case reports and a literature review are presented to emphasize the clinical and roentgenological findings in rhabdomyosarcoma. Misinterpretation of microscopic findings can delay the histological diagnosis. Cross-striations, the "hallmark" of rhabdomyosarcoma, are not always found, while "racquet" and "spindle" cells may be seen. Special stains and electron microscopy can assist the pathologist. The pathological findings of the different variants of rhabdomyosarcoma and a review of cases accessioned by the A.F.I.P. Otolaryngic Registry are presented. Early diagnosis of rhabdomyosarcoma is important because the disease, once inevitably fatal, can now be controlled and apparently cured in most cases by a combination of surgery, radiation, and multidrug chemotherapy. This therapeutic approach, its results, complications, and support measures are considered.

Adolescent↗
PubMed1998

[Comparison of the transcription of the fetal type acetylcholine receptor and myogenin in rhabdomyosarcoma].

Myogenin and the fetal type acetylcholine receptor (AChR) subunits are specific immunohistochemical markers for the diagnosis of rhabdomyosarcomas. In spite of light microscopy and immunohistochemistry, the diagnosis of doubtful cases and small biopsies of rhabdomyosarcomas remains a challenge. Therefore, a PCR-based highly sensitive approach, would be a valuable diagnostic adjunct and should be free from the risk of contamination of the tumor sample with normal tissue. We studied the transcription of myogenin and fetal type AChR in rhabdomyosarcomas, other childhood and adult tumors and normal tissues. In all embryonal and alveolar rahbdomyosarcomas transcripts of both myogenin and fetal type AChR could be detected. The detection of myogenin mRNA however was not specific for rhabdomyosarcomas but occurred in normal muscle and the majority of other normal tissues and childhood tumors. In contrast the transcription of fetal type AChR, which is defined by an alpha subunit AChR/gamma subunit AChR ratio < 1 was encountered only in rhabdomyosarcomas and denervated muscle. Therefore we suggest, that mRNA of the fetal type AChR but not myogenin is a highly specific and sensitive target for the PCR-based diagnosis of rhabdomyosarcomas.

Adult↗
PubMed2000

The use of magnetic resonance imaging in the diagnosis and followup of pediatric pelvic rhabdomyosarcoma.

PURPOSE: Previous radiological descriptions of pelvic rhabdomyosarcoma emphasized ultrasonography and computerized tomography (CT). Few reports are available on the use of magnetic resonance imaging (MRI) for diagnosing and following pelvic rhabdomyosarcoma. We retrospectively compared MRI to CT for diagnosing and following children with pelvic rhabdomyosarcoma. MATERIALS AND METHODS: We treated 4 boys and 3 girls for pelvic rhabdomyosarcoma. Initial and followup evaluations included pelvic CT and MRI at intervals determined by treatment and disease status. We retrospectively reviewed the clinical charts and imaging studies of these patients. The initial radiological report was evaluated and then 1 radiologist reviewed all studies. Attention was directed toward identifying lesions revealed by CT or MRI but not by the other modality. RESULTS: MRI detected all lesions shown by CT. On the other hand, MRI detected residual disease in 1 case that was not demonstrated by CT. In 2 other patients MRI was superior to CT for delineating the local extent of disease, especially urethral involvement. CONCLUSIONS: Compared with CT, MRI improves the detection of residual pelvic rhabdomyosarcoma. Tissue planes are well delineated, allowing more accurate assessment of tumor invasion into adjacent structures. MRI is the imaging modality of choice for following pediatric patients with pelvic rhabdomyosarcoma.

Child↗
PubMed2000

Expression of HER/erbB family of receptor tyrosine kinases and induction of differentiation by glial growth factor 2 in human rhabdomyosarcoma cells.

Five human rhabdomyosarcoma cell lines were used to investigate the surface expression of HER/erbB receptors, particularly of HER-2, HER-3 and HER-4, by flow cytometry. HER-2 was expressed in 3/5 rhabdomyosarcoma cell lines. HER-3 was expressed in all rhabdomyosarcoma cell lines. None of the rhabdomyosarcoma cell lines investigated showed HER-4 surface expression. To study the biological activity of HER/erbB receptors in rhabdomyosarcomas, cells were cultured in the presence of glial growth factor 2 (GGF-2), a specific ligand of HER-3 that is able to stimulate myogenesis in normal myoblasts. In 3 of 3 human rhabdomyosarcoma cell lines positive for both HER-2 and HER-3 receptors, the treatment with GGF-2 induced a significant increase in myogenic differentiation.

Cell Differentiation↗