Interactions between normal and tumoral tissues at the boundary of human anterior pituitary adenomas

Abstract

We studied the boundary between adenoma and peritumoral anterior pituitary tissues in order to understand their mutual interactions during tumour progression. We selected 18 adenomas of different secretory type, grade and invasiveness in which fragments of peritumoral anterior pituitary were still attached to the adenoma. Immunohistochemistry was performed on serial sections with markers of the basement membranes (type IV collagen), the hormone-producing cells of the normal and neoplastic anterior pituitary, and the folliculo-stellate cells (S-100 protein). In passing from tumour to gland, localized areas of passive compression of the normal gland were seen in only 3 cases. In all the tumours, the boundary consisted partly or solely of a transitional zone characterized by the presence of enlarged cell-cords. Openings in the basement membrane of these enlarged cell-cords were seen in contact with the tumour tissue. Normal and neoplastic cells intermingled in the transitional zone. Normal residual cells could be seen in the central area of the tumour but no adenomatous cells were observed in the gland around the tumour. Folliculo-stellate cells were concentrated in the vicinity of the transition zone. These findings favour the existence of an active process of adenoma expansion within the normal parenchyma, without noticeable infiltration of tumour cells into surrounding gland.

Curcumin suppresses HIF1A synthesis and VEGFA release in pituitary adenomas

“…As curcumin was found to suppress VEGFA secretion by FS cells in the normal pituitary (Schaaf et al 2010), it may attenuate the above-mentioned physiological functions of VEGFA, which needs to be clarified in future studies. In pituitary adenomas, FS cells are absent or rare and only very few cases of endocrine-inactive FS cell adenomas have been reported so far (Iwaki et al 1986, Farnoud et al 1994, Hori et al 2009). Therefore, in most endocrine-active or -inactive pituitary adenomas, the tumour cells themselves are capable of producing VEGFA (Lloyd et al 1999, Lohrer et al 2001, Viacava et al 2003.…”

Correlation of VEGF production with IL1α and IL6 secretion by human pituitary adenoma cells

“…FS cells are a potential source of IL1a, and while they are known to secrete IL6, it has not been reported that they secrete IL1a. FS cells are uncommon within an adenoma, and it has been observed that a transition zone rich in FS cells exists between the adenoma and normal tissue (50,51). Lohrer et al (35) proposed that in addition to any other effects IL6 may have, it may enhance the release of VEGF from FS cells in the transition zone, further increasing levels of VEGF in the region.…”

Programmed cell senescence: role of IL-6 in the pituitary

“…IL-6 is produced by tumoral cells themselves but is also delivered to the adenoma cells through IL-6-producing folliculo stellate (FS) cells, which surround or invade the pituitary tumors (Hofler et al 1984, Farnoud et al 1994, Ueta et al 1995, Renner et al 1997, Vajtai et al 2007). IL-6 mRNA and protein levels were also detected in cell cultures of all types of pituitary adenomas (Jones et al 1994, Borg et al 2003, Sapochnik et al 2016.…”

“…stimulates the secretion of ACTH, GH, PRL, LH and FSH , Ray & Melmed 1997, from the anterior lobe in a paracrine manner. A transition zone between normal pituitary tissue and the adenoma that is extremely rich in FS cells has been demonstrated (Farnoud et al 1994). Paracrine IL-6 delivered by FS cells contributes to the development of an adenoma, by promoting tumor cell expansion because of the induction of VEGF release and extracellular matrix-modifying enzymes and tissue inhibitors of metalloproteinases expression (Matsumoto et al 1993), which cause extracellular matrix remodeling and vessel formation (Renner et al 1998).…”