Peptide Growth Factors and Myofibroblasts in Capsules Around Human Breast Implants

Lossing, Clas; Hansson, Hans‐Arne

doi:10.1097/00006534-199306000-00014

Cited by 74 publications

(38 citation statements)

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“…Although p140 trkA and the MAPKs mediate the mitogenic activity of NGF, its anti-apoptotic activity required p75 NTR and NF-B alone. NGF is present in the mammary gland (41,42) as well as its transcripts, 2 and our present finding therefore emphasizes that NGF is a crucial regulator of mammary tumor growth. The inhibition of breast cancer progression through the targeting p140…”

Section: Fig 6 Effect Of Different Neurotrophins On Mcf-7 Cellssupporting

confidence: 76%

Nerve Growth Factor Stimulates Proliferation and Survival of Human Breast Cancer Cells through Two Distinct Signaling Pathways

Descamps

Toillon

Adriaenssens

et al. 2001

Journal of Biological Chemistry

208

209

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We show here that the neurotrophin nerve growth factor (NGF), which has been shown to be a mitogen for breast cancer cells, also stimulates cell survival through a distinct signaling pathway. Breast cancer cell lines (MCF-7, T47-D, BT-20, and MDA-MB-231) were found to express both types of NGF receptors: p140 trkA and p75 NTR . The two other tyrosine kinase receptors for neurotrophins, TrkB and TrkC, were not expressed. The mitogenic effect of NGF on breast cancer cells required the tyrosine kinase activity of p140 trkA as well as the mitogen-activated protein kinase (MAPK) cascade, but was independent of p75 NTR . In contrast, the anti-apoptotic effect of NGF (studied using the ceramide analogue C2) required p75 NTR as well as the activation of the transcription factor NF-kB, but neither p140 trkA nor MAPK was necessary. Other neurotrophins (BDNF, NT-3, NT-4/5) also induced cell survival, although not proliferation, emphasizing the importance of p75 NTR in NGF-mediated survival. Both the pharmacological NF-B inhibitor SN50, and cell transfection with IkBm, resulted in a diminution of NGF anti-apoptotic effect. These data show that two distinct signaling pathways are required for NGF activity and confirm the roles played by p75 NTR and NF-B in the activation of the survival pathway in breast cancer cells. Nerve growth factor (NGF)1 is the archetypal member of the neurotrophin superfamily, which also includes brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), NT-4/5, and NT-6 (1). NGF interacts with two classes of membrane receptor: the TrkA proto-oncogene product p140 trkA , which possesses intrinsic tyrosine kinase activity, and a secondary receptor, p75 NTR , that belongs to the tumor necrosis factor (TNF) receptor family (2). The stimulation of cell survival and cell differentiation by NGF and other neurotrophins have been described primarily in neuronal cell systems (3). Although the neurotrophic effect through p140trkA is known to involve the MAPK cascade, the role of p75 NTR is still controversial; there is evidence that it can both positively and negatively regulate neuronal cell death and differentiation, depending on the cell type examined (4). In some cases, p75NTR is an inducer of apoptosis, even without NGF stimulation (5), whereas in other cases the activation of p75 NTR by NGF results in a protection from cell death (6). In addition to its neurotrophic function, other activities of NGF have been described. For example, NGF can modulate gene expression in monocytes (7), it is chemotactic for melanocytes (8), and its inhibition on p75 NTR can block the migration of Schwann cells (9). NGF also stimulates the proliferation of chromaffin cells (10), lymphocytes (11), and keratinocytes (12). We have previously shown that NGF is mitogenic for cancerous but not normal human breast cells (13), and these data, as well as others showing a role for NGF in the stimulation of prostatic cancer cells (14 -17), implicate NGF in non-neuronal carcinogenesis.Both cellular proliferation as well as tumor c...

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Section: Fig 6 Effect Of Different Neurotrophins On Mcf-7 Cellssupporting

confidence: 76%

Nerve Growth Factor Stimulates Proliferation and Survival of Human Breast Cancer Cells through Two Distinct Signaling Pathways

Descamps

Toillon

Adriaenssens

et al. 2001

Journal of Biological Chemistry

208

209

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“…implants (23). However, in these studies, the source of NGF has not been clarified, although in the mouse it does not seem to be affected by removal of the submaxillary glands, which are known to be a major source of NGF.…”

Section: The Mitogenic Effect Of Ngf On Human Breast Cancer Cells 16661mentioning

confidence: 99%

Nerve Growth Factor Is Mitogenic for Cancerous but Not Normal Human Breast Epithelial Cells

Descamps¹,

Lebourhis²,

Delehedde³

et al. 1998

Journal of Biological Chemistry

108

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We show here that nerve growth factor (NGF), the archetypal neurotrophic factor, is able to stimulate the proliferation of breast cancer cells (MCF-7 and MDA-MB-231 cell lines), although it is unable to stimulate growth of normal breast epithelial cells (NBEC). This stimulation induced cells in the G 0 phase to reenter the cell cycle, as well as shortening cell cycle duration. Immunoblotting experiments revealed that both the two cancer cell lines and the NBEC express high affinity (p140 trk ) and low affinity (p75) NGF receptors. Inhibition of the NGF growth-promoting effect by the drugs K-252a and PD98059 indicated that activation of Trktyrosine kinase activity and the mitogen-activated protein kinase cascade are necessary to obtain the mitogenic effect. Activation of mitogen-activated protein kinase can be detected in breast cancer cells after 10 min of NGF stimulation, whereas no change was detected in NBEC. These results demonstrate that NGF is a mitogenic factor for human breast cancer cells and that it might constitute a new regulator of breast tumor growth.

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“…The presence of myofibroblasts in the contracted capsule is reported to be related to a-smooth muscle actin (a-SMA) production, with more severely deformed capsules displaying a higher a-SMA production, which points to a direct role of activated myofibroblasts in the development of contracture (13). It has also been demonstrated that the number ofmyofibroblasts present in the tissue is proportional to the thickness of the contracture (9).…”

mentioning

confidence: 99%

“…The development of a fibrotic capsule around foreign material is the organism's physiological defence mechanism against material it does not recognize (9)(10). It has been hypothesized that the severity of capsular contracture is directly related to the degree of the local inflammatory reaction (11).…”

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confidence: 99%

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Effects and Zafirlukast on Capsular Contracture: Long-Term Results

Mazzocchi

Dessy

Alfano

et al. 2012

Int J Immunopathol Pharmacol

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Capsular contracture is a distressing complication after breast augmentation for both the patient and surgeon. Although capsular contracture is a multifactorial process, one common denominator in the successful treatment of this complication is believed to be the abatement of inflammation. Leukotriene antagonists have recently emerged as effective prophylactic agents in reactive airway diseases. A prospective study was carried out on 60 female patients (120 prostheses implanted) with mild/severe capsular contracture in at least one breast. The hardness of capsular contracture was assessed by means of the mammary compliance method. Patients received zafirlukast (AccolateTM) for a 6-month period. Mammary compliance was assessed at the start of the study and thereafter monthly, during drug intake and for one year after drug withdrawal. The results show a significant decrease in breast compliance values in the first 6 months, followed by a significant increase one year after the end of drug intake. Indeed, zafirlukast-treated patients displayed a 6.93% reduction in mammary compliance after 1 month, 14.42% after 3 months, 22.05% after 6 months and 22.52% after 7 months (1 month after the withdrawal of the drug). Thereafter, mammary compliance values gradually increased. A 5.47% reduction in mammary compliance was observed 1 year after drug withdrawal. The present study suggests that zafirlukast may be effective in reducing breast capsule distortion in patients with long-standing contracture, though reduced capsular contracture values are strictly related to the duration of drug intake. Capsular contracture is the most common problem and cause of patient dissatisfaction following augmentation mammaplasty and mammary reconstruction with breast implants; the reported rates of this complication range from 0.5 to 59% (1).Every patient who undergoes implantation with an alloplastic implant experiences capsules around the prostheses. Fibrotic tissue promotes compression around the implant, which in tum distorts and deforms the mass, compromising the aesthetic result and causing pain (2-7). Breast firmness that is so marked as to result in a painful, hard breast, on occasion with visible distortion, has been termed fibrous capsular contracture (8). A number of intraoperative and postoperative factors may be linked to capsular contracture. Unfortunately, as few strictly-controlled studies have been conducted to investigate the causes and possible prevention of capsular contracture, there are as yet no definite data on the aetiopathogenesis of this complication (8). Although the pathogenesis of capsular contractere is still unclear, most reports indicate a multifactor explanation (2-6).The development of a fibrotic capsule around

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Peptide Growth Factors and Myofibroblasts in Capsules Around Human Breast Implants

Cited by 74 publications

References 0 publications

Nerve Growth Factor Stimulates Proliferation and Survival of Human Breast Cancer Cells through Two Distinct Signaling Pathways

Nerve Growth Factor Stimulates Proliferation and Survival of Human Breast Cancer Cells through Two Distinct Signaling Pathways

Nerve Growth Factor Is Mitogenic for Cancerous but Not Normal Human Breast Epithelial Cells

Effects and Zafirlukast on Capsular Contracture: Long-Term Results

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